Summary Recommendations
The recommendations of the PROSPECT Working Group are graded A–D, based on the level of evidence from the studies, which is in accordance with the Oxford Centre for Evidence-Based Medicine (CEBM website accessed Dec 2003, Sackett 2000). In the context of PROSPECT, recommendations based on procedure-specific evidence are grade A (randomised clinical trials), those based on transferable evidence are grade B (randomised clinical trials) or grade C (retrospective studies or case series) and those based on clinical practice are grade D. (Click here for further information on levels of evidence and grades of recommendation)
PROSPECT provides clinicians with supporting arguments for and against the use of various interventions in postoperative pain based on published evidence and expert opinion. Clinicians must make judgements based upon the clinical circumstances and local regulations. At all times, local prescribing information for the drugs referred to must be consulted.
The following pre-, intra- and postoperative interventions have been evaluated for the management of postoperative pain following abdominal hysterectomy:
Pre-operativeRecommended:

Single-dose spinal local anaesthetic plus strong opioid, for anaesthetic (grade D) and postoperative analgesic purposes (grade A), but the benefits must be weighed against the risks of the invasive nature of the procedure

This algorithm for managing postoperative pain is based on the PROSPECT recommendations and illustrates the different treatment pathways for low- ¢ and high- ¢ risk patients, as well as describing the steps of the peri-operative pathway/therapies that apply to all patients ¢. Therapies that are not recommend are also indicated.
a Low-risk patients are otherwise healthy patients who are not considered to be at a higher risk than is typically associated with anaesthetic or analgesic agents
b High-risk patients are those considered to be at a high risk of adverse effects from inhalation anaesthetics and high-dose opioids, e.g. those at risk of organ dysfunction or undergoing extensive surgery for malignancy.

The studies showed that LAVH is associated with significantly lower postoperative pain scores than abdominal hysterectomy: meta-analyses showed a reduction of up to 29 mm at 48 h on a 100-mm VAS (p<0.00001) (see Operative Techniques section)

In light of the different pain profiles for LAVH and abdominal hysterectomy, and the absence of studies in LAVH, these procedures will be assessed separately, and an analysis of analgesia for controlling postoperative pain in LAVH conducted when more studies are available

Transferable evidenceAs for all of the procedures in PROSPECT, abdominal hysterectomy-specific evidence was supplemented with transferable evidence, the majority of which was from other major gynaecological and abdominal procedures.

PROSPECT Recommendations

A recommendation of anaesthetic choice based on postoperative analgesic effect cannot be made for abdominal hysterectomy, because there is no evidence for the comparative benefits of different anaesthetic techniques in reducing postoperative pain. Moreover, anaesthetic choice should be based on factors other than the management of postoperative pain, including individual patient risk factors and local practice (Grade D)

General anaesthesia or single shot spinal anaesthesia with or without sedation is recommended for routine use in abdominal hysterectomy, but the continuous epidural catheter technique is not recommended for routine use, based on the relative risks and benefits of these techniques in this patient population (grade D)

Continuous epidural with or without a light general anaesthetic or combined epidural-spinal anaesthesia is recommended over general anaesthesia alone in high-risk patients, e.g. those at risk of organ dysfunction and some patients undergoing extensive surgery for malignancy. In these high-risk patients, the benefits of neuraxial anaesthesia (e.g. reduction in inhalation anaesthetics and opioid use as well as reduced paralytic ileus and improved pulmonary function) outweigh the risks. In these pa

Clinical Practice

The continuous epidural technique produces a less profound block than spinal anaesthesia and takes a longer time to perform as well as conveying a higher risk of rare complications such as epidural haematoma

Transferable Evidence from Other Procedures

Inhaled anaesthesia was similar to combined nitrous oxide/propofol anaesthesia for postoperative pain scores, supplementary analgesic consumption and time to recovery from anaesthetic in patients undergoing laparoscopic hysterectomy Nelskyla et al 1997Click here for more information

Epidural and spinal anaesthesia are not significantly different for: the need for postoperative pain relief, anaesthetic failure rate, need for additional intra-operative analgesia, need for conversion to general anaesthesia, maternal satisfaction and the need for neonatal intervention as determined in a systematic review of caesarean section Ng et al 2004

Abdominal Hysterectomy-Specific Evidence - Study information

Combined general-epidural anaesthetic was superior to general anaesthetic alone for reducing postoperative pain scores in two studies, and one study showed greater postoperative benefits with an additional epidural bolus at closure Jorgensen et al 2001Click here for more information

PROSPECT Recommendations

Intra-operative strong opioids are recommended for the treatment of postoperative pain in hysterectomy based on their analgesic efficacy in the early postoperative period (grade A)

Clinical Practice

[None cited]

Transferable Evidence from Other Procedures

[None cited]

Abdominal Hysterectomy-Specific Evidence - Study information

There is evidence from one of three studies that intra-operative short-acting strong opioid provided a benefit over placebo up to 4 h for reducing postoperative pain scores at rest, but all studies showed no significant benefit at 24 h Katz et al 1996Click here for more information

PROSPECT Recommendations

Intra-operative adenosine is not recommended based on limited evidence of its analgesic efficacy (grade A) and a lack of clinical experience with this agent (grade D)

Intra-operative NMDA-receptor antagonists are not recommended based on inconsistent evidence of their analgesic efficacy and effect on reducing PONV (grade A), as well as a lack of clinical understanding of these agents

Intra-operative benzodiazepines are not recommended based on limited evidence for their analgesic efficacy (grade A)

Intra-operative tryptophan is not recommended based on a lack of analgesic efficacy (grade A)

Clinical Practice

Adenosine and tryptophan are not used routinely because of a lack of clinical experience with these agents

NMDA-receptor antagonists are not used routinely because of the current lack of understanding of their optimum dose, rate and route of administration as well as their cost-benefit relationship; in addition, they are associated with adverse side-effects, e.g. ketamine is known for its toxicity and for causing dysphoria

Overall, NMDA-receptor antagonists provided no significant benefit over placebo in reducing postoperative pain scores, supplementary analgesic consumption or PONV. However, the results were mixed and were independent of the timing of administration Burstal et al 2001Click here for more information

PROSPECT Recommendations

Intra-operative administration of single dose epidural analgesia, in addition to anaesthesia, is not recommended for the treatment of postoperative pain based on evidence of a limited duration of effect in reducing postoperative pain and a lack of benefit in reducing supplementary analgesic consumption (grade A)

A recommendation cannot be made for epidural anaesthesia based on its postoperative analgesic effects because there is no evidence for its relative postoperative analgesic benefits compared with other methods of anaesthesia. Moreover, the choice of anaesthetic regimen should be based on anaesthetic requirement and the relative risks and benefits of the anaesthetic related to the patient and the surgical procedure (grade D) (See Anaesthetic techniques section)

Clinical Practice

Epidural analgesia is associated with a relatively high degree of patient monitoring and rare major complications

Epidural clonidine is not used routinely because it is associated with an increased risk of hypotension, sedation and bradycardia

Transferable Evidence from Other Procedures

Epidural and spinal anaesthesia were not significantly different for: the need for postoperative pain relief, anaesthetic failure rate, need for additional intra-operative analgesia, need for conversion to general anaesthesia, and maternal satisfaction in a systematic review of caesarean section Ng et al 2004

Abdominal Hysterectomy-Specific Evidence - Study information

Intra-operative epidural morphine, with or without postoperative epidural boluses, provided a significant benefit over epidural saline placebo in reducing postoperative pain scores at 6 h, but the results at 12 and 24 h were not significant Jorgensen et al 1982Click here for more information

Intra-operative epidural morphine extended the time to first analgesic request in one study (p<0.05; n=14) Jorgensen et al 1982

PROSPECT Recommendations

Intra-operative wound infiltration is recommended based on specific evidence that it reduces pain following hysterectomy at 8 h (grade A). Although this outcome did not reach clinical significance, this method of analgesia is convenient and has a favourable safety profile Gallagher et al 2001Click here for more information

Clinical Practice

Intra-operative wound infiltration is a well-established method of analgesia with a favourable safety profile

Wound infiltration with local anaesthetic provided no significant benefit over placebo for extending the time to first analgesic request in one study (n=41) Hannibal et al 1996

Wound infiltration with local anaesthetic was not significantly different from placebo for the incidence of PONV in the three studies reporting this parameter (all groups received postoperative strong opioids) Klein et al 2000

Clinical Practice

Transferable Evidence from Other Procedures

Intraperitoneal wound infiltration with local anaesthetic produced a clinically significant decrease in VAS score of 13 mm on a 100-mm scale at 1–4 h in patients undergoing laparoscopic cholecystectomy, from a meta-analysis of 13 studies (p<0.05) Møiniche et al 2000

PROSPECT Recommendations

The type of surgical technique for hysterectomy should be based on factors other than the management of postoperative pain, such as the technical feasibility of the operation, the indication for hysterectomy and operative risk-factors of the patient (grade D)

If the surgical requirements (based on technical feasibility, patient indication for hysterectomy and risk factors) allow, LAVH or VH is recommended over open hysterectomy because it is associated with significantly lower postoperative pain, reduced supplementary analgesic consumption and a shorter recovery time compared with abdominal hysterectomy (grade A)

Clinical Practice

Abdominal rather than transvaginal hysterectomy is indicated in patients who have never been pregnant, who suffer from cancer of the uterus or patients having a uterus size that precludes the transvaginal approach

Transferable Evidence from Other Procedures

[None cited]

Abdominal Hysterectomy-Specific Evidence - Study information

LAVH provided a significant benefit over abdominal hysterectomy for reducing postoperative pain scores over the first week following surgery, providing a reduction in 100-mm VAS scores of 16 mm at 24 h, 24 mm at 48 h and 18 mm at 1 week Hwang et al 2002Click here for more information

PROSPECT Recommendations

Active patient warming is recommended in high-risk patients because there is evidence that it reduces intra-operative bleeding (grade A) and improves outcome in high-risk patients (grade D); however, it has no analgesic benefit (grade A)

Leaving the peritoneum open is not recommended over the conventional technique of peritoneal closure because there is evidence that it has no significant analgesic benefit (grade A)

Routine use of drains is not recommended, despite some evidence for an analgesic benefit in laparoscopic hysterectomy, because there is a lack of specific evidence, and a risk of infection and patient dissatisfaction (grade D)

Wet dressings are not recommended over conventional dressings because there is not yet sufficient evidence to support their benefit in reducing postoperative pain (grade A)

It is recommended that the choice of surgical incision for hysterectomy is based on surgical requirements (dependent on the technical feasibility of the operation, the indication for hysterectomy and operative risk-factors of the patient) rather than postoperative pain outcome. If allowed by the surgical requirements, a transverse incision is recommended over a vertical incision because it is associated with lower postoperative pain and less pulmonary dysfunction, while it is has a similar morbi

Diathermy is recommended over the scalpel for hysterectomy incisions based on lower postoperative pain and opioid use as well as greater speed of incision and less blood loss, as shown in patients undergoing elective midline laparotomy (grade B)

Clinical Practice

A transverse incision is the preferred method for hysterectomy for safety and cosmetic reasons. However, a vertical incision may be required where large fibroids need to be removed or where the upper abdomen must be explored. Pulmonary complications are also less likely with transverse incisions

Wound drains are invasive and can increase the risk of infection and, in addition, their extraction is associated with significant patient anxiety

Transferable Evidence from Other Procedures

Drains were superior to no drains for reducing postoperative shoulder-tip pain at 24 h (p=0.01) and 48 h (p=0.018) (non-significant at 3 h), and for reducing abdominal pain at 48 h (p=0.007) (non-significant at 3 and 24 h); but the results were not significant for back pain at any time, in LAVH Shen et al 2003Click here for more information

The Pfannenstiel incision decreased the operating time and hospital stay without affecting morbidity and mortality compared with the vertical incision - as shown in two retrospective studies of surgery for uterine cancer, which did not assess postoperative pain (n=332; n=113) Horowitz et al 2003

Active patient warming and prevention of intra-operative hypothermia decreases the risk of wound infection, hospitalisation time and the incidence of morbid cardiac events in high-risk patients, in a review Leslie et al 2003

Abdominal Hysterectomy-Specific Evidence - Study information

Operative time was significantly shorter for the unsutured compared with the conventional sutured peritoneum (n=66; n=144) Behtash et al 2001

Wet film dressing showed a marginally significant benefit over conventional dressing at day 3 for reducing postoperative pain scores (p=0.046; n=30), but this result was non-significant at all other times Briggs 1996

Unsutured and sutured peritoneum techniques were not significantly different for postoperative pain scores at rest or for supplementary analgesic consumption, for up to 5 days following the operation (n=66; n=144) Behtash et al 2001

There was no significant benefit of active intra-operative warming over placebo for reducing postoperative pain scores or supplementary analgesic consumption for the 48-h study period (n=41) Persson et al 2001

Wet film dressing was not significantly different from conventional dressing for supplementary analgesic consumption (n=30) Briggs 1996

PROSPECT Recommendations

Intra-operative music played to the patient during general anaesthesia is recommended based on its effects in reducing postoperative pain scores, supplementary analgesic consumption and rehabilitation time (grade A)

Therapeutic suggestions and electroacupuncture are not recommended based on their lack of analgesic efficacy (grade A)

Clinical Practice

[None cited]

Transferable Evidence from Other Procedures

[None cited]

Abdominal Hysterectomy-Specific Evidence - Study information

Intra-operative music was superior to placebo for reducing postoperative pain scores on the first postoperative day (p<0.001) (non-significant on the second and third day) (n=58) Nilsson et al 2001

Intra-operative music was superior to placebo for reducing supplementary analgesic consumption on the day of surgery (p=0.028), and there was a trend towards significance on the first postoperative day (p=0.057; n=89) Nilsson et al 2001

Intra-operative music was superior to placebo for time to sitting (p=0.008; n=89) Nilsson et al 2001

Of six studies, all showed no significant benefit of intra-operative therapeutic suggestions over placebo for reducing postoperative pain scores for up to 5 days Block et al 1991

PROSPECT Recommendations

Pre-operative local anaesthetic infiltration at the proposed site of incision is not recommended for abdominal hysterectomy because of its lower benefit compared with post-incisional infiltration for reducing postoperative pain in hysterectomy (grade A). Post-incisional wound infiltration is recommended (see Intra-operative Wound Infiltration)

Pre-incisional wound infiltration provided no significant benefit over placebo for extending the time to first analgesic request in one study (n=41) Hannibal et al 1996

Pre-incisional wound infiltration was not significantly different from post-incisional administration for reducing postoperative pain scores within 0–96 h in two studies Click here for more information

Pre-incisional wound infiltration was not significantly different from post-incisional administration for reducing supplementary analgesic consumption within 0–96 h in two studies Click here for more information

PROSPECT Recommendations

Pre-operative cognitive intervention for patients undergoing hysterectomy is recommended based on its effect on reducing postoperative pain, analgesic consumption and anxiety as well as increasing patient satisfaction (grade A)

Homeopathic arnica and self-relaxation techniques are not recommended based on their lack of analgesic efficacy (grade A)

Data are available from studies that assessed pre-operative analgesia versus pre-operative placebo, as well as those that examine the concept of pre-emptive – or preventive – analgesia, assessed pre-operative analgesia versus the same analgesia given postoperatively. However, a previous systematic review of pre-emptive analgesia for acute or chronic postoperative pain relief in a variety of surgical procedures – such as orthopaedic, dental, gynaecological and abdominal – has concluded that there is no benefit of pre-emptive over postoperative administration (Møiniche 2002). Nevertheless, it is considered that analgesic medication needs to be initiated in time to ensure an adequate analgesic effect in the immediate postoperative period. This may necessitate administration prior to the postoperative period.

PROSPECT Recommendations

Pre- and postoperative gabapentin is recommended (Grade A) for its procedure-specific effects in reducing postoperative opioid use and postoperative nausea

Further studies are required before it is possible to recommend a specific dose or regimen for administration (single or repeated doses)

Procedure-specific and transferable evidence suggests that gabapentin may be associated with sedation, and it is recommended (Grade B) that this side effect should be considered when determining the dose that will be administered

Clinical Practice

[None cited]

Transferable Evidence from Other Procedures

Two systematic reviews and a meta-analysis evaluated the use of gabapentin for postoperative analgesia and demonstrated significant reductions in postoperative pain and supplementary analgesic requirements compared with inactive controls Dahl et al 2004

Abdominal Hysterectomy-Specific Evidence – Study information

Two studies out of two showed a significant reduction in pain scores following pre- and postoperative oral gabapentin + rofecoxib administration compared with placebo following abdominal hysterectomy Gilron et al 2005Click here for more information

Qualitative analysis demonstrated that in three out of four studies there was no significant difference in the incidence of adverse effects following pre- and postoperative oral gabapentin administration compared with placebo Dierking et al 2004

Quantitative analysis showed that there was a significantly lower incidence of nausea in gabapentin group compared with the placebo group Click here for more information

PROSPECT Recommendations

Pre-operative COX-2-selective inhibitors for hysterectomy are recommended because they have an analgesic effect postoperatively (grade A). However, there is no procedure-specific evidence that pre-operative administration of COX-2-selective inhibitors is more effective than postoperative administration

Clinical studies investigating the response to oral challenge with COX-2-selective inhibitors in patients with aspirin-induced asthma have demonstrated that COX-2-selective inhibitors do not have an effect on respiratory function Bavbek et al 2004

Hypersensitivity reactions and serious skin reactions (e.g. toxic epidermal necrolysis, Stevens-Johnson syndrome, and erythema multiforme) can occur with all COX-2-selective inhibitors. Serious skin reactions have been reported in association with valdecoxib at a higher rate than with other COX-2-selective agents EMEA 2004a

Conventional NSAIDs and COX-2-selective inhibitors have been associated with an increased risk of transient hepatotoxicity. Cases of acute hepatic failure have also been reported. Elderly females, with autoimmune disease, and taking other potentially hepatotoxic drugs, may be most susceptible O'Connor et al 2003

Short-term use of COX-2-selective inhibitors or conventional NSAIDs can increase the risk of transient renal impairment, especially in patients with existing renal dysfunction, and both types of agent have been associated with cases of acute renal failure in high-risk patients Cheng et al 2004

Although there is some concern that COX-2-selective inhibitors may impair wound healing, evidence from animal and clinical studies is conflicting Blomme et al 2003

Abdominal Hysterectomy-Specific Evidence - Study information

A pre-operative single bolus of IV parecoxib was superior to placebo for postoperative pain scores on sitting up over 24 h (p=0.02), providing a mean drop of 14 mm in VAS scores on a 100-mm scale (n=36) Ng et al 2003

Compared with the conventional NSAID diclofenac, pre-operative rofecoxib was associated with significantly less intra-operative blood loss (p=0.01) and a lower decrease in haemoglobin (p=0.01) in a group of patients undergoing abdominal or vaginal hysterectomy (n=25) Hegi et al 2004

A pre-operative single bolus of rofecoxib or parecoxib did not significantly reduce postoperative pain scores at rest compared with placebo within 0–24 h in two studies (n=40; n=36) Celik et al 2003

PROSPECT Recommendations

Pre-operative conventional NSAIDs are not recommended because there is evidence that pre-operative administration of conventional NSAIDs is no more effective than postoperative administration (grade A). Moreover, pre-operative administration of these agents can increase the risk of intra- and postoperative bleeding (grade A)

A randomised controlled trial showed that three conventional NSAIDs (diclofenac, ketorolac and ketoprofen) were associated with a similar incidence of surgical site bleeding after elective surgery Forrest et al 2002

Conventional NSAIDs and COX-2-selective inhibitors have been associated with an increased risk of transient hepatotoxicity. Cases of acute hepatic failure have also been reported. Elderly females, with autoimmune disease, and taking other potentially hepatotoxic drugs, may be most susceptible O'Connor et al 2003

Short-term use of conventional NSAIDs or COX-2-selective inhibitors can increase the risk of transient renal impairment, especially in patients with existing renal dysfunction, and both types of agent have been associated with cases of acute renal failure in high-risk patients Cheng et al 2004

The combination of paracetamol with a conventional NSAID was superior to a higher dose of paracetamol alone, administered as a single pre-operative rectal dose for VAS pain scores at rest at 4 h (p<0.05), but there was no significant difference at 2 h and 6–24 h (n=46) Beck et al 2000b

Pre-operative conventional NSAIDs provided no significant benefit over placebo for extending the time to first analgesic request in two out of the three studies that reported this parameter Scott et al 1994Click here for more information

Pre-incisional administration of flurbiprofen was associated with a shorter time to first analgesic request compared with post-incisional administration of a conventional NSAID, in one study (p<0.05; n=30) Nakayama et al 2001b

Pre-incisional administration of conventional NSAIDs conferred no significant benefit over post-incisional administration for the incidence of PONV in two studies (n=65, n=30) Gabbott et al 1997

PROSPECT Recommendations

Pre-incisional administration of strong opioids is not recommended because of the lack of effect in reducing postoperative pain and supplementary analgesic consumption compared with placebo, and the lack of benefit over post-incisional administration of strong opioids (grade A). Moreover, post-incisional strong opioids are significantly more effective for reducing postoperative pain compared with a similar dose of pre-incisional strong opioids (grade A)

PROSPECT Recommendations

Pre-operative clonidine is not recommended based on its limited analgesic efficacy (grade A) and risk of side effects (grade D)

NMDA-receptor antagonists are not recommended based on inconsistent evidence of their analgesic efficacy (grade A), lack of clinical understanding of these agents, and the risk of side effects (grade D)

Benzodiazepines are not recommended based on their lack of analgesic efficacy (grade A)

Clinical Practice

Clonidine is not used routinely for postoperative analgesia, despite its analgesic efficacy, because of the risk of hypotension, sedation and bradycardia

NMDA-receptor antagonists are not used routinely because of the current lack of understanding of their optimum dose, rate and route of administration as well as their cost-benefit relationship; in addition, they are associated with adverse side-effects, e.g. ketamine is known for its toxicity and for causing dysphoria

Pre-operative benzodiazepines provided no significant benefit in reducing postoperative pain scores, and there is evidence that they have a limited effect on reducing supplementary analgesic consumption Caumo et al 2002Click here for more information

NMDA-receptor antagonists provided no significant benefit over placebo in reducing postoperative pain scores, supplementary analgesic consumption or PONV in the majority of studies, but the results were mixed and were independent of the specific type of agent and timing of administration Burstal et al 2001Click here for more information

PROSPECT Recommendations

Pre-operative administration of single dose epidural analgesia, in addition to that required for anaesthetic purposes, is not recommended for the treatment of postoperative pain following hysterectomy, based on specific evidence that pre-operative epidural analgesia is not as effective as postoperative epidural analgesia (grade A)

A recommendation cannot be made for epidural anaesthesia based on its postoperative analgesic effect because there is no evidence for its relative postoperative analgesic benefits compared with other methods of anaesthesia. Moreover, the choice of anaesthetic regimen should be based on anaesthetic requirement and the relative risks and benefits of the anaesthetic related to the patient and the surgical procedure (grade D) (See Anaesthetic techniques section)

Despite the analgesic benefits of pre-operative epidural clonidine, it is not recommended for treating postoperative pain following abdominal hysterectomy because of the incidence of hypotension, sedation and bradycardia (grade D)

Clinical Practice

Epidural analgesia is associated with a relatively high degree of patient monitoring and rare major complications

Epidural clonidine is not used routinely because it is associated with an increased risk of hypotension, sedation and bradycardia

Transferable Evidence from Other Procedures

Epidural and spinal anaesthesia are not significantly different for: the need for postoperative pain relief, anaesthetic failure rate, need for additional intra-operative analgesia, need for conversion to general anaesthesia, and maternal satisfaction as determined in a systematic review of caesarean section Ng et al 2004

PROSPECT Recommendations

Pre-operative single-shot spinal analgesia with local anaesthetic and strong opioid reduces postoperative pain scores and opioid consumption for up to 24 h (grade A). However, these benefits should be weighed against the risks associated with the invasive nature of this technique

Pre-operative single-shot spinal local anaesthetic plus strong opioid can be used, with or without sedation, as an alternative to general anaesthesia (Grade A). However, the choice of anaesthetic regimen should be based on anaesthetic requirement and the relative risks and benefits of the anaesthetic related to the patient and the surgical procedure (Grade D) (see Anaesthetic techniques section)

Spinal neostigmine is not recommended based on limited evidence for its analgesic efficacy, evidence of an associated increase in PONV (grade A) and a lack of clinical experience with this agent (grade D)

Clinical Practice

There is limited clinical experience of spinal neostigmine

Transferable Evidence from Other Procedures

Spinal and epidural anaesthesia are not significantly different for: the need for postoperative pain relief, anaesthetic failure rate, need for additional intra-operative analgesia, need for conversion to general anaesthesia, and maternal satisfaction as determined in a systematic review of caesarean section Ng et al 2004

There is evidence from one of two studies showing a significant benefit of pre-operative spinal neostigmine over placebo for extending the time to first analgesic request (p<0.05; n=92) Lauretti et al 1998a

PROSPECT Recommendations

The choice of anaesthetic regimen should be based on anaesthetic requirement and the relative risks and benefits of the anaesthetic related to the patient and the surgical procedure, rather than on the management of postoperative pain (grade D)

Combined spinal-epidural anaesthesia is a recommended alternative to epidural plus light general anaesthesia for hysterectomy in high-risk patients (grade D), and may have a greater analgesic efficacy compared with epidural alone as shown in caesarean section (grade B)

Abdominal Hysterectomy-Specific Evidence

PROSPECT Recommendations

Pre- and postoperative gabapentin is recommended (Grade A) for its procedure-specific effects in reducing postoperative opioid use and postoperative nausea

Further studies are required before it is possible to recommend a specific dose or regimen for administration (single or repeated doses)

Procedure-specific and transferable evidence suggests that gabapentin may be associated with sedation, and it is recommended (Grade B) that this side effect should be considered when determining the dose that will be administered

Clinical Practice

[None cited]

Transferable Evidence from Other Procedures

Two systematic reviews and a meta-analysis evaluated the use of gabapentin for postoperative analgesia and demonstrated significant reductions in postoperative pain and supplementary analgesic requirements compared with inactive controls Dahl et al 2004

Abdominal Hysterectomy-Specific Evidence - Study information

Two studies out of two showed a significant reduction in pain scores following pre- and postoperative oral gabapentin + rofecoxib administration compared with placebo following abdominal hysterectomy Gilron et al 2005Click here for more information

Qualitative analysis of three out of four studies demonstrated that there was no significant difference in the incidence of adverse effects following pre- and postoperative oral gabapentin administration compared with placebo Dierking et al 2004

Quantitative analysis showed that there was a significantly lower incidence of nausea in gabapentin group compared with the placebo group Click here for more information

PROSPECT Recommendations

COX-2-selective inhibitors are recommended for their effect in reducing supplementary analgesic use (grade B). They should be given in combination with strong opioids for high-intensity pain, or with weak opioids for moderate- or low-intensity pain (grade D)

In patients receiving postoperative epidural analgesia, it is recommended that COX-2-selective inhibitors are used only if analgesia is inadequate (grade B) (see Postoperative, Conventional NSAIDs section)

COX-2-selective inhibitors may be preferred to conventional NSAIDs in the peri-operative setting, in patients who have an increased risk of bleeding, or who are at risk of gastroduodenal ulcer/erosion (grade B)

Clinical studies investigating the response to oral challenge with COX-2-selective inhibitors in patients with aspirin-induced asthma have demonstrated that COX-2-selective inhibitors do not have an effect on respiratory function Bavbek et al 2004

Hypersensitivity reactions and serious skin reactions (e.g. toxic epidermal necrolysis, Stevens-Johnson syndrome, and erythema multiforme) can occur with all COX-2-selective inhibitors. Serious skin reactions have been reported in association with valdecoxib at a higher rate than with other COX-2-selective agents EMEA 2004a

Conventional NSAIDs and COX-2-selective inhibitors have been associated with an increased risk of transient hepatotoxicity. Cases of acute hepatic failure have also been reported. Elderly females, with autoimmune disease, and taking other potentially hepatotoxic drugs, may be most susceptible O'Connor et al 2003

Short-term use of COX-2-selective inhibitors or conventional NSAIDs can increase the risk of transient renal impairment, especially in patients with existing renal dysfunction, and both types of agent have been associated with cases of acute renal failure in high-risk patients Cheng et al 2004

Abdominal Hysterectomy-Specific Evidence

PROSPECT Recommendations

Conventional NSAIDs are recommended for their analgesic and opioid-sparing effects (grade A). They should be given in combination with strong opioids for high-intensity pain, or with weak opioids for moderate- or low-intensity pain (grade D)

In patients receiving epidural analgesia, it is recommended that conventional NSAIDs are used only if analgesia is inadequate (grade B)

Conventional NSAIDs are not recommended in patients who have an increased risk of bleeding, or who are at risk of gastroduodenal ulcer/erosion (grade B)

A randomised controlled trial showed that three conventional NSAIDs (diclofenac, ketorolac and ketoprofen) were associated with a similar incidence of surgical site bleeding after elective surgery Forrest et al 2002

Conventional NSAIDs and COX-2-selective inhibitors have been associated with an increased risk of transient hepatotoxicity. Cases of acute hepatic failure have also been reported. Elderly females, with autoimmune disease, and taking other potentially hepatotoxic drugs, may be most susceptible O'Connor et al 2003

Short-term use of conventional NSAIDs or COX-2-selective inhibitors can increase the risk of transient renal impairment, especially in patients with existing renal dysfunction, and both types of agent have been associated with cases of acute renal failure in high-risk patients Cheng et al 2004

There was no significant difference between postoperative ketorolac and morphine each given by IM PCA for reducing postoperative pain scores at the doses studied (both study groups were allowed rescue morphine) (n=29) Black et al 1990

IV PCA administration of strong opioids is recommended based on its greater analgesic efficacy, lower opioid load and greater patient satisfaction compared with regular (fixed-interval) or on-request dosing in hysterectomy and other procedures (grade A); however, fixed-interval IV administration titrated to pain intensity is also recognised as an effective mode of administration (grade D)

IM administration of strong opioids is not recommended based on the pain associated with these injections (grade D)

To minimise the dose of strong opioids, and associated side-effects, it is recommended that strong opioids are combined with COX-2-selective inhibitors or conventional NSAIDs, plus paracetamol (grade B) (see respective sections)

There are not currently enough data to make a recommendation for other modes of administration of strong opioids, such as intra-nasal or slow-release tablets

Transdermal patches are not recommended: they are not approved for routine use due to the risk of opioid accumulation (grade D)

Clinical Practice

Strong opioids are considered to be an effective analgesic for postoperative pain following abdominal hysterectomy, but, because of their adverse effects, they are generally used in combination with non-opioid analgesics to minimise the opioid

IM administration of strong opioids is considered to be more painful than IV administration. However, the dose and rapidity of IV administration should be assessed to minimise the risk of respiratory depression

Transdermal patches are not approved for routine use because of the risk of opioid accumulation

Continuous infusions of strong opioids by PCA, on top of PCA bolus doses, are being used less frequently as a precaution against opioid accumulation

Transferable Evidence from Other Procedures

Opioids administered by PCA decreased the risk of pulmonary complications and patients preferred them compared with regular IM, IV or subcutaneous opioid treatment, although there was no significant difference for pain scores, as determined in a quantitative systematic review of randomised trials in various surgical procedures Walder et al 2001

Sufentanil provided a significant benefit over morphine for reducing postoperative pain scores at rest and on movement for the first 2 h following initiation of PCA, but there was no significant difference for the remaining 24 h Ginsberg et al 2000Click here for more information

There is mixed evidence for the benefit of PCA compared with regular/on-request IM administration of strong opioids for reducing overall opioid consumption, although one study suggests that they produced different patterns of dosing Thomas et al 1995Click here for more information

The incidence of PONV was not significantly different between PCA and IM morphine, in two studies reporting this parameter (n=126, n=22) Choiniere et al 1998

IV pethidine was superior to intranasal pethidine for reducing postoperative pain scores at 5–80 min (p<0.05) and for reducing the total amount of pethidine consumed (p<0.05), in one study (n=60) Striebel et al 1993

Oral slow-release and IM morphine were similar for postoperative pain scores, supplementary analgesic consumption and the incidence of PONV in two studies (n=38; n=30) Fell et al 1982

Morphine gave a numerically longer time to first analgesic request than tramadol in one study reporting this parameter, although the result did not reach statistical significance Coetzee et al 1998

Different strong opioids were not significantly different from each other, for reducing postoperative pain scores, supplementary analgesia and PONV, in the majority of studies assessing different strong opioid regimens Chui et al 1992Click here for more information

Bolus IV PCA plus background infusion of morphine was associated with a consistently greater consumption of morphine than IV PCA alone but the results did not reach statistical significance, in two studies (n=20, n=20) El-Falaki et al 2000

PROSPECT Recommendations

Weak opioids are recommended based on evidence for their analgesic efficacy in gynaecological and abdominal surgery, as well as in other procedures (grade B). Weak opioids should be combined with COX-2-selective inhibitors or conventional NSAIDs and paracetamol, for controlling moderate- (VAS<50>30) or low-intensity (VAS £30) pain later in the postoperative period (grade D)

Clinical Practice

It is considered that maximum doses of weak opioids have a plateau of effect on controlling high-intensity pain (VAS³ 50) following abdominal hysterectomy and that strong opioids should be used instead; weak opioids are considered to be effective for lower intensity pain later in the postoperative period

Weak opioids and conventional NSAIDs had a similar effect of reducing supplementary analgesic consumption in one study reporting this parameter (n=130) Torres et al 2001

Conventional NSAIDs and weak opioids have a similar effect for prolonging the time to first analgesic request in one study reporting this parameter (n=58) Ilias et al 1996

Tramadol 50 mg IV administered postoperatively on request gave numerically lower postoperative pain scores than placebo, but this was not statistically significant, in one study (n=40) Ilias et al 1996

Tramadol 50 mg IV administered postoperatively on request gave a numerically longer time to first analgesic request than placebo but this was not statistically significant in one study (n=80) Ilias et al 1996

PROSPECT Recommendations

Paracetamol is recommended for moderate- (VAS<50>30 mm) or low-intensity (VAS £30 mm) pain, in combination with COX-2-inhibitors or conventional NSAIDs, based on its mild analgesic and opioid-sparing effect following hysterectomy (grade A)

However, paracetamol is not recommended for high-intensity pain (VAS³ 50 mm) because it has no additional analgesic benefit over that conferred by NSAIDs following abdominal gynaecological procedures (grade B)

Clinical Practice

Paracetamol is a well-established analgesic for mild-to-moderate pain (VAS <50 mm) and has a favourable safety profile

Transferable Evidence from Other Procedures

There was no benefit of paracetamol with NSAID compared with NSAID alone for reducing pain scores in a meta-analysis of results from a variety of surgical procedures including dental, orthopaedic and gynaecological operations Rømsing et al 2002

PROSPECT Recommendations

NMDA-receptor antagonists are not recommended based on inconsistent evidence of their analgesic efficacy (grade A), lack of clinical understanding of these agents, and the risk of side-effects (grade D)

Benzodiazepines are not recommended based on their lack of analgesic efficacy (grade A)

Other agents, such as pentazocine, clomipramine, delta-9-tetrahydrocannabinol and naloxone cannot be recommended for postoperative analgesia based on limited evidence for their analgesic efficacy (grade A) and a lack of clinical experience with these agents (grade D)

Clinical Practice

NMDA-receptor antagonists are not used routinely because of the current lack of understanding of their optimum dose, rate and route of administration as well as their cost-benefit relationship. In addition, they are associated with adverse side-effects, e.g. ketamine is known for its toxicity and for causing dysphoria

There is limited clinical experience of using pentazocine, clomipramine, delta-9-tetrahydrocannabinol and naloxone for analgesic purposes

NMDA-receptor antagonists provided no significant benefit over placebo in reducing postoperative pain scores, supplementary analgesic consumption or PONV in the majority of studies, but the results were mixed and were independent of the timing of administration Burstal et al 2001Click here for more information

PROSPECT Recommendations

Continuous postoperative epidural infusion is not recommended for routine use in hysterectomy patients because its analgesic benefits compared with systemic analgesia are short-lasting and are of marginal clinical significance (up to 4 h) (grade A). Therefore, the risks of the epidural technique outweigh the analgesic benefits in low-risk patients (grade D)

Continuous postoperative epidural analgesia with local anaesthetic plus strong opioid is recommended in high-risk patients (e.g. those at risk of organ dysfunction and some patients undergoing extensive surgery for malignancy) – and in these patients it is recommended that the epidural is also used for anaesthesia – because the benefits of the epidural technique, e.g. reduction in inhaled anaesthetics and systemic opioids as well as reduced paralytic ileus and improved pulmonary function (grade

Despite the analgesic benefits of epidural clonidine, it is not recommended to control postoperative pain following abdominal hysterectomy because of the incidence of hypotension (grade A), sedation and bradycardia (grade D)

Clinical Practice

Epidural analgesia is associated with a relatively high degree of patient monitoring and rare major complications

Transferable Evidence from Other Procedures

Epidural analgesia using local anaesthetic was superior to systemic strong opioid for reducing postoperative pain scores in six studies identified in a systematic review of abdominal surgery Jorgensen et al 2000b

Epidural analgesia using a combination of local anaesthetic and strong opioid was superior to local anaesthetic alone for reducing postoperative pain – 15 mm reduction in VAS score on a 100-mm scale – in a meta-analysis of five studies in abdominal surgery Jorgensen et al 2000b

Epidural analgesia using local anaesthetics was superior to epidural opioids or systemic opioids for reducing the incidence of postoperative gastrointestinal paralysis, in a systematic review in abdominal surgery Jorgensen et al 2000b

Abdominal Hysterectomy-Specific Evidence - Study information

Postoperative epidural ropivacaine was superior to placebo for reducing postoperative pain scores at rest and on coughing within 0–2, 0–4 and 4–12 h, but results at 2–22 h were non-significant (n=104) Chinachoti et al 2002

Epidural bupivacaine was superior to ropivacaine for reducing supplementary ketorolac consumption and gave a larger spread of sensory block than ropivacaine, while recovery outcomes were not significantly different Jorgensen et al 2000aClick here for more information

There is evidence for a limited benefit of epidural clonidine over epidural morphine for reducing postoperative pain scores, but two of two studies showed that clonidine causes hypotension Lund et al 1989Click here for more information

PROSPECT Recommendations

Postoperative wound infiltration administered by PCA may have a benefit in controlling postoperative pain, but there is not currently enough evidence to recommend it. However, intra-operative wound infiltration is recommended (grade A) (see Intra-operative Wound Infiltration)

Clinical Practice

Intra-operative wound infiltration is a well-established method of analgesia with a favourable safety profile. However, methods of postoperative wound infiltration are not well established

Transferable Evidence from Other Procedures

[None cited]

Abdominal Hysterectomy-Specific Evidence - Study information

Postoperative wound infiltration administered by PCA with a 1-h lockout showed a significant benefit of reducing postoperative pain scores on coughing and when raising leg at 4 h (p=0.006 and p=0.009 respectively); however, these comparisons at 1–3 and 5–24 h were non-significant, and results at rest showed no significant benefit at all times (n=36) Zohar et al 2001

A systematic search of the literature between January 2004 and June 2006 identified additional studies of interventions in abdominal hysterectomy, as listed in this folder, together with brief summaries of the study outcomes and a comment from the PROSPECT Working Group regarding the impact of the recent evidence on the recommendations. Additional details of the studies will be included in the main review text at the next full update of the evidence and recommendations.

In one study, time to first request for rescue analgesia was significantly longer, and total analgesic consumed was less, following pre-operative conventional NSAID administration, compared with placebo (Akarsu 2004); in another study, PCA morphine consumption was significantly reduced in the group receiving pre-operative conventional NSAID at 2, 4, 6, 12 and 24 h compared with the saline control group (Karaman 2006)

In one study there was a significantly higher incidence of nausea and vomiting in the placebo group compared with the pre-operative conventional NSAID group (Akarsu 2004). In two studies there were no significant differences between the incidence of adverse events in the conventional NSAID and placebo groups (Bikhazi 2004; Karaman 2006)

In one study peri-operative COX-2-selective inhibitor, alone and in combination with gabapentin, significantly reduced postoperative VAS pain scores at rest at 20, 24, 28, 32, 44, 48, 52 and 56 h compared with placebo; VAS pain scores at sitting were significantly reduced in the COX-2-selective inhibitor plus gabapentin group at 20h, and following the COX-2-selective inhibitor both alone and in combination with gabapentin at 24, 28, 32, 44, 48, 52, and 56 h compared with placebo; VAS pain scores at peak expiration were significantly reduced following administration of the COX-2-selective inhibitor alone and in combination with gabapentin at 20, 24, 28, 32, 44, 48, 52, and 56 h compared with placebo; VAS pain scores during coughing were significantly reduced in the COX-2-selective inhibitor plus gabapentin group at 20, 24, 28, 32 h, and following administration of the COX-2-selective inhibitor both alone and in combination with gabapentin at 44, 48, 52 and 56 h, compared with placebo (Gilron 2005)

Three out of three studies showed COX-2-selective inhibitor superior to placebo for reducing supplementary analgesic consumption

Total and incremental supplementary analgesic consumptions were significantly less in the pre-operative COX-2-selective inhibitor group compared with placebo at 1, 2, 4, 6, 8, and 12 h postoperatively (Karamanlioglu 2004)

Cumulative morphine consumption was significantly less in the COX-2-selective inhibitor plus gabapentin group compared with placebo at 2, 3, 4, 8, 20, 24, 28 and 32 h postoperatively, and interval morphine consumption was significantly less in the COX-2-selective inhibitor group at 4–8, 8–20, 20–32, 32–44 and 44–56 h and in the COX-2-selective inhibitor plus gabapentin group at all time points recorded after surgery, compared with placebo (Gilron 2005)

PCA morphine requirement was significantly less following administration of the COX-2-selective inhibitor, alone and in combination with gabapentin at 1, 8, 12, 16, 24, and 30 h postoperatively, and at 20 h following the COX-2-selective inhibitor plus gabapentin, compared with placebo (Turan 2006)

Three out of three studies showed that COX-2-selective inhibitors are not superior to placebo for reducing the incidence of adverse effects

In two studies there was no significant difference in the incidence of adverse events between the COX-2-selective inhibitor group and control (Gilron 2005; Karamanlioglu 2004)

In one study there was no significant difference between COX-2 inhibitor alone or gabapentin alone compared with placebo, but there was a significantly lower incidence of nausea in the combination of COX-2-selective inhibitor and gabapentin group compared with the placebo group (Turan 2006)

One study showed that pre-operative oral clonidine did not significantly reduce pain scores both at rest and during movement compared with placebo at all time points assessed (Oofuvong 2005); one study showed that pre- and postoperative oral clonidine significantly reduced pain scores compared with placebo at all time points assessed (Hidalgo 2005)

One study showed that intra-operative dexmedetomidine had no effect on pain scores at rest and during movement compared with placebo, both in the PACU and 0–48 h after surgery (Gurbet 2006)

Morphine consumption was not significantly different between clonidine and placebo groups at all time points assessed (Hidalgo 2005; Oofuvong 2005)

Patients in the intra-operative dexmedetomidine group consumed significantly less postoperative morphine compared with the placebo group, both in the PACU and 0–48 h after surgery (Gurbet 2006)

Systemic clonidine: no change to recommendation Dexmedetomidine: limited data, so not recommended at the current time

One study showed that pre-operative morphine did not significantly reduce subjective pain scores (0–10) compared with saline control (Goldstein 2005)

One study showed that postoperative IV morphine significantly reduced VRS pain scores compared with placebo 2 min after administration, but not at any other time point assessed (5, 10 and 15 min) (Larijani 2004)

One study showed a significant reduction in supplemental analgesic demands between 15 and 30 min postoperatively, cumulative PCA demands, cumulative pethidine consumption after the first 24 h, and additional pethidine consumption during the first 2 h, in the intraoperative pethidine group compared with the postoperative pethidine group (Mavioglu 2005)

One study demonstrated a significant reduction in PCA morphine requirements at 1, 2, 3, 4, 8, 12, 16, 20 and 24 h after surgery in the postoperative tramadol group compared with the saline control group (Kocabas 2005)

One study showed that pre-operative spinal morphine significantly reduced VAS pain scores at rest and during coughing at all time points assessed (up to 20 h post-surgery) compared with control (no treatment) (Karaman 2006)

One study showed that postoperative total morphine consumption and PCA demands were significantly lower in the group receiving intra-operative spinal morphine compared with the IV morphine group during postoperative 24 h (Togal 2004)

One study showed that pre-operative antihistamine, combined with either a 1.2:1 or a 4.8:1 ratio of antihistamine-morphine mixture for postoperative PCA, did not significantly reduce VAS pain scores at rest or supplemental analgesic requirements at any time point assessed (0–24 h) compared with saline control (Lin 2005)

One study showed that patients in the pre-operative antihistamine alone group consumed significantly less morphine at 3, 6, 12, and 24 h postoperatively compared with patients in the postoperative antihistamine alone and saline control groups (Chia 2004)

One study showed that pre- and intra-operative beta-blockers had no effect on VAS pain scores at rest and during movement at all time points assessed compared with saline control (Chia 2004)

Patients receiving beta-blockers consumed significantly less PCA morphine at all time points assessed, and the mean total morphine consumption was significantly less, compared with saline control (Chia 2004)

One study showed that intra-operative single bolus wound instillation (topically on to peritoneum for 10 min) significantly reduced NRS pain scores at 60 min after surgery compared with placebo (pain assessed every 15 min from 0–120 min after surgery; all other time points not significantly different) (Heid 2005)

There were no differences in cumulative morphine consumption or adverse effects observed between the wound instillation and placebo groups (Heid 2005)

Time to first analgesic request was significantly longer, and total supplementary analgesic consumption was significantly lower, in the IP LA + IP conventional NSAID + IP weak opioid group compared with the IP LA + IP conventional NSAID group and the IP LA + IP weak opioid group (Pirbudak 2004)

One study showed that there were no significant differences in analgesic efficacy between pre-operative and postoperative epidural analgesia (LA + ketamine) (DeCastro 2005)

One study showed that there were no significant differences in VAS pain scores at rest and during coughing (at 4, 8, and 21 h), or total morphine consumption, between the postoperative epidural 0.1% ropivacaine + fentanyl group and the postoperative epidural 0.2% ropivacaine group (Thienthong 2004)

PROSPECT provides clinicians with supporting arguments for and against the use of various interventions in postoperative pain based on published evidence and expert opinion. Clinicians must make judgements based upon the clinical circumstances and local regulations. At all times, local prescribing information for the drugs referred to must be consulted.Grades of recommendation (GoR) are assigned according to the overall level of evidence (LoE) on which the recommendations are based, which is determined by the quality and source of evidence.

Grades of recommendation (GoR) based on source and level of evidence (LoE): Summary table

The AGREE II instrument (Brouwers 2010) is used internationally to assess the methodological rigour and transparency of practice guidelines. As far as possible, the methodology of the PROSPECT C-Section review meets the requirements of ‘Domain 3: Rigour of development’ of the AGREE II instrument:

Systematic methods were used to search for evidence.

The criteria for selecting the evidence are clearly described.

The strengths and limitations of the body of evidence are clearly described.

The methods for formulating the recommendations are clearly described.

The health benefits, side effects, and risks have been considered in formulating the recommendations.

There is an explicit link between the recommendations and the supporting evidence.

The guideline has been externally reviewed by experts prior to its publication. [The evidence and recommendations will be submitted for peer-review after publication on the PROSPECT website]

A procedure for updating the guideline is provided. [Methodology is provided so that the systematic review can be updated as required]

·Non-closure of the peritoneum is recommended (GoR A)
based on procedure-specific evidence for postoperative analgesia (LoE 1)

Intraoperative interventions that are
recommended for C-Section

Note:
Unless otherwise stated, ‘intra-operative’ refers to interventions applied
after incision and before wound closure. In C-Section, ‘post-delivery’ refers
to administration after the umbilical cord is clamped and the baby is
delivered.

Note:
Analgesics should be administered at the appropriate time
(pre- or intra-operatively) to provide sufficient analgesia in the early
recovery period

Wound infiltration with LA or TAP blocks or
iliohypogastric/ilioinguinal blocks

Surgical technique

Transverse incision†

Non-closure of peritoneum

Postoperative

Oral paracetamol + oral NSAID + systemic opioid as
rescue

Continuous wound infusion with LA

* IT morphine/epidural opioids are recommended, but alternative
analgesic techniques such as wound infiltration with LA, TAP block,
iliohypogastric and ilioinguinal blocks should be considered to avoid the
potential opioid-related side effects of neuraxial opioids

# IV paracetamol and IV NSAIDmay not be necessary if
neuraxial opioids are used

† Amongst transverse
incisions, the Joel-Cohen incision and similar modifications are superior to
the Pfannenstiel incision for outcomes related to postoperative pain

Wound infiltration with LA or TAP blocks or
iliohypogastric/ilioinguinal blocks

Surgical technique

Transverse incision†

Non-closure of peritoneum

Postoperative

Oral paracetamol + oral NSAID + systemic opioid as
rescue

Continuous wound infusion with LA

* IT morphine/epidural opioids are recommended, but alternative
analgesic techniques such as wound infiltration with LA, TAP block,
iliohypogastric and ilioinguinal blocks should be considered to avoid the
potential opioid-related side effects of neuraxial opioids

# IV paracetamol and IV NSAIDmay not be necessary if
neuraxial opioids are used

† Amongst transverse
incisions, the Joel-Cohen incision and similar modifications are superior to
the Pfannenstiel incision for outcomes related to postoperative pain

For each review, a Subgroup of the PROSPECT Working Group performs an initial evaluation of the evidence and also drafts clinical practice statements and recommendations, which are then discussed by the whole Working Group before a final consensus is reached.
For the C-Section review, the Subgroup members were:

Professor Marc Van De Velde (PROSPECT Working Group member)

Professor Girish Joshi (PROSPECT Working Group member)

Professor Narinder Rawal (PROSPECT Working Group member)

Dr Thomas Jaschinski (IFOM - Institut für Forschung in der Operativen Medizin, Universität Witten/Herdecke, Köln, Germany) provided support in conducting the literature search, preparing the evidence summary and coordinating the Subgroup and Working Group reviews of the evidence to prepare the final recommendations.
The recommendations for postoperative pain management in C-Section were voted on by nine Working Group members to show the strength of consensus. The results of each vote are indicated within the PROSPECT recommendations sub-folders.

C-Section: Sources and levels of evidence (LoE) determine the grades of recommendation (GoR)

GoR are assigned according to the overall LoE, which is determined by the quality of studies cited, the consistency of evidence and the source of evidence:C-Section: levels of evidence and grades of recommendationSources of evidence in PROSPECTThe evidence for prospect is derived from three separate sources, and this evidence is taken into consideration by the prospect Working Group to determine the prospect recommendations:

Procedure-specific evidence derived from the systematic reviews of the literature

Transferable evidence from comparable procedures, or from other relevant sources, identified by the members of the prospect Working Group

Current practice – A commentary on the interventions from the members of the prospect Working Group

Practical prospect recommendations are based on all the information

Study quality assessmentFor the C-Section review, the quality of procedure-specific evidence has been assessed according to NICE methodology, to determine the possibility of selection bias, performance bias, attrition bias and detection bias (http://www.nice.org.uk/article/pmg6b).

Quality indicators used to determine the LoE of individual studies:

Allocation concealment: indicates whether there was adequate prevention of foreknowledge of treatment assignment by those involved in recruitment (in the table below, A=adequate, B=unclear, C=inadequate, D=not used). Empirical research has shown that trials with inadequate or unclear allocation concealment report significantly greater estimates of treatment effect than those trials in which concealment was adequate (Chalmers 1983, Schulz 1995, Moher 1998). Allocation concealment was found to be more important for preventing bias than other aspects of study quality, such as generation of the allocation sequence and double-blinding (Chalmers 1983, Schulz 1995, Moher 1998, HigginsandGreen 2005, http://handbook.cochrane.org/)

Statistical analyses and patient follow-up: indicates whether statistical analyses were reported, and whether patient follow-up was greater or less than 80%.

Numerical scores (total 1–5) for study quality: assigned using the method proposed by Jadad 1996, to indicate whether a study reports appropriate randomisation, double-blinding and statements of possible withdrawals. Empirical research found that low-quality trials were associated with an increased estimate of treatment benefit compared with high-quality trials (Moher 1998)

No meta-analyses were performed due to a limited number of studies of homogeneous design that reported similar outcome measures. Therefore, the procedure-specific evidence was only assessed qualitatively.

Transferable evidence has not been included in the C-Section review as there was sufficient procedure-specific evidence on which to base the recommendations for the most common analgesic interventions.

PROSPECT Recommendations

C-Section-Specific Evidence

The administration of oral gabapentin 300 mg 2 h before surgery during spinal anaesthesia (without fentanyl) was superior to placebo capsule combined with fentanyl 10 µg during spinal anaesthesia for pain relief and time to first analgesic request Najafi Anaraki and Mirzaei 2014

PROSPECT Recommendations

Pre-operative dexamethasone cannot be recommended at this time (GoR D) based on limited procedure-specific evidence

Consensus agreement 100% (9/9)

C-Section-Specific Evidence

Dexamethasone 10 mg given intravenously before surgery decreased postoperative pain with movement at 1 h, 6 h, 12 h and 24 h, but not at 2 h and 3 h, compared with placebo. Although the cumulative incidence of PONV was significantly lower in women receiving dexamethasone, there were no significant differences in PONV at specific assessment time points Cardoso et al 2013

Intravenous dexamethasone 8 mg administered before skin incision was superior to placebo in pain scores at rest and on movement between 6 and 24 h, but not before. However, there was no significant difference in the consumption of supplemental analgesia Wu et al 2007

PROSPECT Recommendations

There is no evidence of analgesic benefit to recommend general anaesthesia over neuraxial anaesthesia (i.e., epidural anaesthesia, spinal anaesthesia, and combined spinal epidural anaesthesia), due to lack of direct comparative studies focusing on postoperative analgesia (GoR D). However, neuraxial anaesthesia techniques are recommended for safety reasons (e.g., neuraxial anaesthesia obviates the need for airway manipulation and avoids the postoperative sedative effects of general anaesthetics)

Consensus agreement 100% (9/9)

C-Section-Specific Evidence

Three studies comparing CSEA with EA showed a significant reduction in pain scores with CSEA during or after surgery but the results related to the time to first analgesic request were inconsistent Davies et al 1997Click here for more information

A systematic review comparing the efficacy and side effects of SpA and EA showed no differences in unplanned interventions for pain relief postoperatively. However, there was an increased need for treatment for hypotension in women undergoing SpA Ng et al 2004

A systematic review comparing the effects of regional anaesthesia with those of GA showed (based upon one RCT) that the time to first request for analgesia was longer with EA compared with GA. There were no significant differences in the Apgar scores at 1, 5 and 10 min Afolabi and Lesi 2012

CSEA with epidural volume extension (EVE) was not superior to SpA in reducing intraoperative pain scores and the time to first analgesic request Lew et al 2004

One study showed a significant reduction in the time to first analgesic request for the SpA group compared with the CSEA group. However, there was no significant difference in supplemental analgesic use Thorén et al 1994

PROSPECT Recommendations

Intrathecal morphine below 200 µg is recommended if the patient has received spinal anaesthesia (GoR A) based on procedure-specific evidence for improved postoperative analgesia (LoE 1)

However, due to opioid-related side effects, including delayed respiratory depression, alternative analgesic techniques should be considered

Consensus agreement 100% (9/9)

Epidural opioids are recommended if the patient has received epidural anaesthesia (GoR A) based on procedure-specific evidence for improved postoperative analgesia (LoE 1)

However, due to opioid related side effects, including delayed respiratory depression, alternative analgesic techniques should be considered

Consensus agreement 100% (9/9)

C-Section-Specific Evidence: Epidural or IT Analgesia With Anaesthesia

Fewer patients receiving IT morphine 100 µg during surgery requested supplemental analgesia compared with patients receiving postoperative oral oxycodone, but there was no significant difference in pain scores or consumption of supplemental analgesia and IT morphine was associated with a higher incidence of pruritus McDonnell et al 2010Click here for more information

The combination of IT morphine 0.2 mg with spinal bupivacaine compared with spinal bupivacaine alone prolonged the time to first analgesic request. However, women receiving IT morphine reported nausea and pruritus significantly more often Abouleish et al 1988

The time to first PCA demand was longer in each of four groups receiving IT morphine (0.1, 0.2, 0.3, 0.4 mg) in combination with SpA bupivacaine than in the control group (0 mg morphine). The IT morphine groups showed a significantly lower total PCA morphine demand in the first 24 hours than the control group. There were no significant differences between mean VAS scores Girgin et al 2008

Postoperative pain was significantly lower in a group receiving IT morphine added to SpA with bupivacaine than in a group receiving saline plus SpA. Morphine consumption was significantly lower in the IT morphine group Swart et al 1997

The addition of IT morphine 0.2 mg to hyperbaric bupivacaine 0.5% for SpA compared with hyperbaric bupivacaine alone reduced postoperative pain scores, the need for additional analgesia and prolonged the time to first analgesic request Terajima et al 2003

The administration of IT morphine 0.25 mg or 0.1 mg during SpA was superior to saline for postoperative pain relief. However, the higher dose of IT morphine was associated with significantly increased occurrence of pruritus Abboud et al 1988

The coadministration of IT sufentanil 5 µg and IT morphine 100 µg was superior to IT sufentanil 5 µg plus a single injection of s.c. morphine 10 mg for postoperative pain relief and consumption of supplemental analgesia Draisci et al 2009

Women undergoing caesarean delivery with CSEA benefited from the additional administration of IT morphine (0.1 and 0.2 mg) to 15 mg of spinal levobupivacaine. It prolonged the time to the first analgesic request compared with saline; however, there were no significant differences in postoperative pain scores Unlugenc et al 2012

Time to first analgesic request was significantly shorter following epidural diamorphine 3 mg (2 boluses) administration compared with IT morphine 0.2 mg. However, IT morphine was associated with higher incidence of PONV Caranza et al 1999

Similar pain relief was achieved with the administration of PCEA pethidine compared with IT morphine during surgery plus IV pethidine via PCA or IT morphine during surgery plus postoperative oral paracetamol and codeine. Patients receiving epidural pethidine had a trend for higher pain scores but also lower nausea and pruritus scores Paech et al 2000

CSEA with hyperbaric bupivacaine plus sufentanil 5 µg and epidural lidocaine combined with either epidural morphine or IT morphine produced similar postoperative pain relief and similar time to first analgesic demand. However, women receiving epidural morphine had a decreased 24 h morphine consumption Dualé et al 2003

A randomised controlled study comparing IT morphine 100 µg, IT morphine 200 µg and epidural morphine 3 mg showed no significant differences in postoperative pain scores and the time to first request for rescue analgesia Sarvela et al 2002

The combination of neostigmine 12.5 µg and morphine 50 µg administered with SpA with 0.5% hyperbaric bupivacaine 12 mg had a prolonged analgesic effect compared with either neostigmine or morphine alone Chung et al 1998Click here for more information

IT morphine 0.1 mg was superior in postoperative pain relief, supplemental need for analgesia and time to first analgesic request compared with IT fentanyl 25 µg, when combined with IT hyperbaric bupivacaine Siti Salmah and Choy 2009

IT ketamine 0.1 mg/kg added to spinal bupivacaine compared with bupivacaine alone prolonged intraoperative anaesthesia, increased the time to the first analgesic request and decreased the total analgesic consumption in the first 24 postoperative hours Khezri et al 2013

The addition of dextromethorphan to different doses of IT morphine was not superior to placebo combined with the same doses of IT morphine for pain relief. Higher doses of morphine were associated with a significantly increased incidence of PONV and pruritus Choi et al 2003

Spinal morphine 0.1 mg combined with IV ketorolac was not superior to different doses of spinal morphine (0.1 mg or 0.2 mg) or IV ketorolac alone in terms of pain relief and time to first analgesic request Cohen et al 1996

The administration of IT fentanyl 25 µg was superior to IT ketamine 0.05 mg/kg, both added to plain bupivacaine for spinal analgesia, for providing postoperative pain relief and prolonging the time to first analgesic request Unlugenc et al 2006

The comparison of either IT morphine 0.1 mg or diamorphine 0.25 mg in combination with SpA using hyperbaric bupivacaine and fentanyl 12.5 µg showed no differences in postoperative pain relief, time of first PCA use or cumulative morphine requirement postoperatively Barkshire et al 2001

There were no significant differences between groups receiving either morphine 0.1 mg or 0.2 mg combined with IT 0.5% bupivacaine 2.5 mL in VAS pain scores and time to first analgesic request Milner et al 1996

Epidural morphine was superior to placebo for pain relief, duration of pain relief and reduction of additional analgesics. However, patients in the morphine group reported pruritus significantly more frequently Binsted 1983

A systematic review of RCTs comparing epidural morphine with parenteral opioids showed that a single bolus of epidural morphine provides better pain relief than parenteral opioids but with an effect limited to the POD 1 and with an increase in morphine side effects Bonnet et al 2010

There were no significant differences in pain scores, morphine consumption and time to first analgesic request between butorphanol 2 mg IV (with epidural saline) and epidural butorphanol 2 mg (plus saline IV), but both regimens provided superior analgesia to saline placebo in the first 2 h postoperatively Camann et al 1992

Epidural morphine 5 mg compared with IV morphine 5 mg was superior for reducing the need for supplemental analgesics and prolonging the time to first analgesic request. However, significantly more patients receiving epidural morphine experienced pruritus Cohen and Woods 1983

Fentanyl (20 µg, 10 min lockout) administered via PCEA compared with the same dose via IV PCA resulted in lower pain scores at rest at 8, 12, 24 h, but not at 0.5 and 4 h and in lower pain scores on coughing at 8 and 12 h, but not at remaining points in time. There was no significant difference in PONV between the two groups, but patients receiving fentanyl via PCEA experienced pruritus significantly more frequently Cooper et al 1995

The administration of epidural fentanyl via PCA was superior to IV morphine via PCA in pain scores at rest 4 and 8 h, but not at recovery, 12 and 21 h as well as in lower pain scores on coughing at 4, 8 and 21 h, but not at remaining assessment times. The incidence of PONV and drowsiness was significantly lower in patients receiving epidural fentanyl via PCA Cooper et al 1999

Epidural morphine was superior to IM morphine in pain relief and the need for morphine consumption. The two groups were similar in the occurrence of PONV and pruritus Daley et al 1990

The administration of sufentanil PCEA was superior to morphine iPCA in reducing pain at rest at 30 min and 2 h, but not between 6 h and POD 2 and in reducing pain on movement at POD 2, but not on POD 1. The incidence of PONV was similar between the two groups, but patients receiving epidural sufentanil experienced pruritus significantly more frequently Grass et al 1994

PCEA administration reduced drug consumption within 24 h compared with IV PCA administration for both pethidine and fentanyl. The number of PCA demands was lower with pethidine than fentanyl. Patients preferred PCEA to IV PCA administration for pethidine but not fentanyl Ngan Kee et al 1997

There was no significant difference between the incidence of PONV, sedation and dizziness in the epidural pethidine group and IM pethidine group. However, patients receiving epidural pethidine had lower pain scores during the first 2 h Perriss et al 1990

The duration of analgesia was significantly longer in patients receiving epidural diamorphine 3 mg compared with IM morphine 10 mg. However, only the pain score at 5 hours was lower in the diamorphine group Stevens et al 1991

The administration of epidural diamorphine was superior to IV diamorphine via PCA for pain scores at 1 and 2 h, but not between 4 and 48 h. The incidence of pruritus and PONV was similar between the two groups Stoddart et al 1993

The administration of fentanyl or bupivacaine plus fentanyl administered via PCEA was superior to bupivacaine alone via PCEA in pain scores at rest at 12 h, but not at 0.5, 4, 8 and 24 h. There were no significant differences between the three groups in pain scores on coughing at any assessment time. However, the incidence of pruritus was significantly lower in patients receiving only bupivacaine compared with the two other groups Cooper et al 1996

The administration of PCEA pethidine compared with IT morphine during surgery plus IV pethidine via PCA or IT morphine during surgery plus postoperative oral paracetamol and codeine produced similar pain relief at most time points. Patients receiving epidural pethidine had a trend towards higher pain scores but also lower nausea and pruritus scores Paech et al 2000

The duration of analgesia was significantly longer in patients receiving epidural morphine compared with epidural fentanyl, buprenorphine or butorphanol. However, the incidence of pruritus was significantly higher in the morphine and fentanyl groups Ackerman et al 1989

Epidural butorphanol produced a longer duration of analgesia with less pruritus than epidural sufentanil, but pain scores of patients receiving sufentanil were significantly lower Bansal et al 2009

Epidural morphine was superior to epidural fentanyl for duration of analgesia. However patients that received fentanyl had significantly lower pain scores during the first two hours, but not afterwards Blanco et al 1987

The epidural administration of morphine 4 mg and combination of morphine 2 mg plus sufentanil 25 µg was superior compared to sufentanil 50 µg in pain relief between 2 and 12 h, but not before. Patients receiving sufentanil 50 µg required more frequent supplementary analgesia. The incidence of pruritus and PONV did not differ between the three groups; however, dizziness was only observed in patients receiving sufentanil alone or in combination with morphine Dottrens et al 1992

PCEA administration reduced drug consumption within 24 h compared with IV PCA administration for both pethidine and fentanyl. The number of PCA demands was lower with pethidine than fentanyl. Patients preferred PCEA to IV PCA administration for pethidine but not fentanyl Ngan Kee et al 1997

Epidural sufentanil delivered by PCA with a concomitant infusion of either sufentanil or saline produced similar pain scores overall, with significantly less pain at 6 h in the sufentanil infusion group, but not at 0,12, 18 and 24h. The incidence of PONV did not differ between the groups Vercauteren et al 1995

The administration of PCEA pethidine compared with IT morphine during surgery plus IV pethidine via PCA or IT morphine during surgery plus postoperative oral paracetamol and codeine produced similar pain relief at most time points. Patients receiving epidural pethidine had a trend towards higher pain scores but also lower nausea and pruritus scores Paech et al 2000

PROSPECT Recommendations

Neuraxial clonidine is not recommended (GoR D), although procedure-specific evidence suggests it provides superior analgesia, because of side effects (e.g. hypotension)

Consensus agreement 100% (9/9)

C-Section-Specific Evidence

The comparison of three doses of IT clonidine (150 µg, 300 µg and 450 µg) demonstrated a dose-dependent effect. A higher dose was significantly associated with lower pain scores and a delayed request for supplemental analgesics Filos et al 1994

Epidural infusion of clonidine (400 µg bolus plus 10 µg/h) and (800 µg bolus plus 20 µg/h) compared with placebo prolonged the time to first analgesic request. Only the high-dose clonidine group needed less morphine via iPCA compared with the placebo group Mendez et al 1990

Analgesia with bupivacaine (0.06 mg/cm body height) plus clonidine (75 µg) or plus clonidine and fentanyl (12.5 µg) was superior to bupivacaine alone. Time to first analgesic request was significantly prolonged following anaesthesia with bupivacaine, clonidine and fentanyl compared with the other groups. Intraoperative nausea-vomiting was more frequent in the group given bupivacaine alone Benhamou et al 1998

The administration of IT clonidine 150 µg was superior to placebo in terms of postoperative pain relief and time to first analgesic request. However, the side effects sedation, hypotension and dryness of mouth were more frequent in the clonidine group Filos et al 1992

Spinal bupivacaine combined with sufentanil 2 µg and 75 µg clonidine was superior to sufentanil 2 µg alone and 150 µg clonidine alone in the time to first analgesic request. However, there was no significant difference among the three groups in postoperative pain scores and in the need for supplemental analgesia Lavand'homme et al 2008

C-Section-Specific Evidence

Joel-Cohen-based compared with Pfannenstiel caesarean section techniques were associated with lower duration of postoperative pain and with less use of analgesia Hofmeyr et al 2008

The Joel-Cohen incision was significantly superior to the Pfannenstiel incision for operative time, postoperative pain, postoperative need for supplemental analgesia, time to get out from bed and time to walk straight without support Abuelghar et al 2013

A systematic review of RCTs comparing different abdominal incisions showed that the Joel-Cohen incision was superior to the Pfannenstiel approach in reducing postoperative analgesic requirements, total dose of analgesia in the first 24 h and in increasing the time to first analgesic request Mathai et al 2013

A systematic review showed that there is little information available to inform the choice of the most appropriate surgical technique for uterine incision and uterine closure to adopt Dodd et al 2008

PROSPECT Recommendations

Non-closure of the peritoneum is recommended (GoR A) based on procedure-specific evidence for postoperative analgesia (LoE 1)

Consensus agreement 100% (9/9)

C-Section-Specific Evidence

A systematic review evaluating the effects of non-closure as an alternative to closure of the peritoneum showed that the number of postoperative analgesic doses was reduced in the peritoneal non-closure group Bamigboye and Hofmeyr 2003

Non-closure of both the visceral and the parietal peritoneum produced a significant reduction in pain scores and need for supplemental analgesia compared with closure Tabasi et al 2013

Non-closure and closure of the parietal peritoneum showed no differences in duration of surgery and postoperative pain scores. However, the non-closure group had a significantly reduced requirement for supplemental analgesia as well as shorter time to mobilisation and oral intake Altinbas et al 2013

PROSPECT Recommendations

C-Section-Specific Evidence

Rectal naproxen followed by oral naproxen compared with placebo reduced postoperative pain scores, especially on the first day after surgery, reduced the need for additional analgesics and prolonged the time to first analgesic request Angle et al 2002

Rectal diclofenac 100 mg every 12 h led to less morphine consumption compared with placebo. However, pain scores were similar between the two groups Dahl et al 2002

The use of diclofenac suppository 100 mg compared to no suppository reduced the need for ropivacaine and fentanyl given via PCEA from 6 to 18 h, but not from 0 to 6 h and not from 18 to 24 h. There was no significant difference between the two group in pain scores on movement Lim et al 2001

The postoperative administration of paracetamol and diclofenac was not superior to diclofenac alone and to paracetamol alone in pain scores at rest and on movement. However, patients receiving the combination of paracetamol and diclofenac needed significantly less morphine given via iPCA compared with paracetamol alone, but not compared with diclofenac. The groups did not differ in time to first independent ambulation Munishankar et al 2008

Administration of rectal diclofenac (3x 50 mg) was superior to placebo for reducing the need for supplemental analgesia. Postoperative pain was lower in patients receiving diclofenac during the first 3 h, but not afterwards Olofsson et al 2000

The administration of intravenous ketorolac (</=120 mg/day) compared with placebo reduced the consumption of meperidine for 24 h, but not afterwards. The pain relief was similar between the two groups Pavy et al 2001

Diclofenac suppository 100 mg after surgery followed by 3 additional doses at 8 h intervals was superior to pethidine 1 mg/kg IM after surgery followed by three additional doses at 8 h intervals for pain relief at 10 h, 18 h and 26 h, but not at 2 h. The incidence of PONV was similar between the two groups, but patients receiving pethidine reported dizziness significantly more frequently Soroori et al 2006

The administration of diclofenac 75 mg IM every 12 h for 2 doses compared to no intervention reduced the need for rescue analgesia and produced significantly lower pain scores Surakarn and Tannirandorn 2009

Postoperative ketorolac 30 mg IM and postoperative pethidine 75 mg IM showed similar analgesic efficacy and time to first analgesic request, although more side-effects were noted in the pethidine group Gin et al 1993

There were no significant differences in postoperative pain scores and supplemental analgesic use between the intravenous paracetamol group versus oral ibuprofen group Alhashemi et al 2006

The administration of oral valdecoxib 20 mg every 12 h for 72 h compared with placebo was not superior in pain relief, need for supplemental analgesics and time to first analgesic request Carvalho et al 2006

Spinal morphine 0.1 mg combined with IV ketorolac was not superior to different doses of spinal morphine (0.1 mg or 0.2 mg) or IV ketorolac alone in terms of pain relief and time to first analgesic request Cohen et al 1996

The administration of subcutaneous pethidine 1 mg/kg followed by subcutaneous pethidine 1 mg/kg with metoclopramide 10 mg IM every 8 h for three days was superior to oral diclofenac sodium 75 mg twice daily in terms of the need for rescue analgesia. However, both groups were not different in pain scores and incidence of PONV Marzida 2009

PROSPECT Recommendations

Ketamine cannot be recommended at this time (GoR D) based on inconsistent procedure-specific evidence

Consensus agreement 100% (9/9)

C-Section-Specific Evidence

The administration of IV low-dose ketamine as an adjuvant to bupivacaine for spinal anaesthesia was associated with longer postoperative analgesia and a reduced need for analgesia consumption than bupivacaine alone Menkiti et al 2012

The administration of IV ketamine 0.2 mg/kg before the induction of anaesthesia decreased postoperative pain scores, the need for supplemental analgesia and prolonged the time to first analgesic request Ghazi-Saidi and Hajipour 2002

Women receiving IM S-ketamine 0.5 mg/kg followed by a 2 µg/kg/min IV continuous infusion over 12 h had a prolonged time to first analgesic request and a reduced cumulative morphine consumption compared with placebo. However, ketamine was associated with a significantly increased incidence of drowsiness, diplopia, nystagmus, dizziness, light-headness, positive dysphoria and vomiting Suppa et al 2012

The addition of IV ketamine compared to placebo for postoperative analgesia showed no benefit in time to first analgesic request, incidence of breakthrough pain and supplemental analgesics Bauchat et al 2011

The IV use of different doses of ketamine (0.25 mg/kg, 0.5 mg/kg, 1 mg/kg) compared with placebo produced similar postoperative pain scores and need for supplemental analgesia Bilgen et al 2012

The administration of IV ketamine 0.5 mg/kg before the skin incision and infused continually at 0.25 mg/kg/h until the end of surgery was not superior to placebo in postoperative pain relief and supplemental fentanyl consumption Han et al 2013

C-Section-Specific Evidence

The administration of subcutaneous pethidine 1 mg/kg followed by subcutaneous pethidine 1 mg/kg with metoclopramide 10 mg IM every 8 h for three days was superior to oral diclofenac sodium 75 mg twice daily for the need for rescue analgesia. However, both groups were not different in pain scores and incidence of PONV Marzida 2009

Postoperative ketorolac 30 mg IM and postoperative pethidine 75 mg IM showed similar analgesic efficacy and time to first analgesic request, although more side-effects were noted in the pethidine group Gin et al 1993

Diclofenac suppository 100 mg after surgery followed by another three doses at 8 h intervals was superior to pethidine 1 mg/kg IM after surgery followed by another three doses at 8 h intervals for pain relief at 10 h, 18 h and 26 h, but not at 2 h. The incidence of PONV was similar between the two groups, but patients receiving pethidine experienced dizziness significantly more frequently Soroori et al 2006

Pain relief was significantly greater in the group receiving oral oxycodone-paracetamol compared with the group receiving morphine via iPCA for 12 h and oral oxycodone-paracetamol after 12 h Davis et al 2006

The administration of piritramide via iPCA versus oral oxycodone was similar in terms of pain scores, need for supplemental anagesics and in the incidence of PONV Dieterich et al 2012

Subcutaneous and IM morphine produced a similar incidence of side effects and pain scores at rest, but pain scores on movement were reduced in the subcutaneous morphine group at 12, 16 and 20 h Safavi and Honarmand 2007

PROSPECT Recommendations

C-Section-Specific Evidence

There were no significant differences in postoperative pain scores and supplemental analgesic use between the IV paracetamol group and the oral ibuprofen group

The administration of IV paracetamol at the end of surgery and every 6 h for 24 h was superior to placebo for pain scores at 6, 12 and 24 h and for consumption of rescue analgesia Omar and Issa 2011

The postoperative administration of paracetamol and diclofenac was not superior to diclofenac alone and to paracetamol alone in pain scores at rest and on movement. However, patients receiving the combination of paracetamol and diclofenac needed significantly less morphine given via iPCA compared with paracetamol alone, but not compared with diclofenac. The groups did not differ in time to first independent ambulation Munishankar et al 2008

Ilioinguinal and iliohypogastric nerve block with 0.5% ropivacaine was superior to nerve block with saline for pain scores at rest at 6, 8, 12, and 24 h and with movement at 6 and 8 h and led to a decreased supplemental analgesia need without increasing side effects Sakalli et al 2010

Ilioinguinal nerve block with 0.5% bupivacaine was superior to no nerve block for pain scores at 0, 4, 8 and 24 h while consumption of supplemental analgesia was decreased Bunting and McConachie 1988

PROSPECT Recommendations

C-Section-Specific Evidence

US-guided TAP block compared with no block significantly reduced postoperative morphine consumption. There were no differences between the groups in pain scores at rest and on moving, sedation level and PONV Tan et al 2012

PROSPECT Recommendations

TENS is not recommended (GoR D) based on limited procedure-specific evidence

Consensus agreement 78% (7/9)

C-Section-Specific Evidence

IV morphine-PCA combined with Hi-TENS significantly reduced the consumption of morphine compared with IV morphine-PCA alone. However, there were no significant differences in pain scores between the two groups Binder et al 2011

TENS versus placebo-TENS was superior for pain relief at rest and on movement. There was no difference in the request for additional analgesics Smith et al 1986

TENS was superior to placebo-TENS for pain relief at 8 h after delivery and associated with a reduced need for supplemental analgesia Kayman-Kose et al 2014

The addition of ketorolac to subcutaneous wound instillation of bupivacaine compared with bupivacaine resulted in lower pain scores on movement, but not at rest. However, the addition of hydromorphone to LA wound instillation did not significantly decrease postoperative pain scores at all. The use of supplemental analgesics was significantly lower in the group with additional ketorolac compared to the only bupivacaine group Carvalho et al 2013

Ropivacaine wound instillation via an elastometric pump was superior to sterile water in the reduction of postoperative morphine consumption. Pain scores at rest did not differ between the groups during the first 6 h. However, patients receiving ropivacaine had lower pain scores during coughing and leg raising between 3 and 6 h, but not before Fredman et al 2000

Epidural levobupivacaine was superior to levobupivacaine administered via subfascial catheter in reducing pain scores at rest during the first 4 hours, but not afterwards. However, pain scores at walking and consumption for opioids were similar between the groups Ranta et al 2006

The IV system with morphine 10 mg and ketorolac 120 mg was more effective than continuous infusion of 0.2% levobupivacaine in reducing the need for supplemental analgesic and in reducing pain scores Magnani et al 2006

For each review, a Subgroup of the prospect Working Group performs an initial evaluation of the evidence and also drafts clinical practice statements and recommendations, which are then discussed by the whole Working Group before a final consensus is reached. The Subgroup may sometimes include a non-Working Group member, to provide additional expertise in the procedure being reviewed.

For the colonic resection surgery review (update 2009), the Subgroup members were:

PROSPECT provides clinicians with supporting arguments for and against the use of various interventions in postoperative pain based on published evidence and expert opinion. Clinicians must make judgements based upon the clinical circumstances and local regulations. At all times, local prescribing information for the drugs referred to must be consulted.

Summary Recommendations

Pre-, intra- and postoperative interventions have been evaluated for the management of postoperative pain following colonic resection. Unless otherwise stated, ‘pre-operative’ refers to interventions applied before surgical incision, ‘intra-operative’ refers to interventions applied after incision and before wound closure, ‘postoperative’ refers to interventions applied at or after wound closure. The following pre-, intra- and postoperative interventions have been evaluated, for the management of postoperative pain following open colonic resection:

Pre-operative

Recommended:

Systemic analgesia

COX-2-selective inhibitors (Grade B) (only for patients who do not receive epidural analgesia)

Continuous administration of pre-/intra-operative IV lidocaine if continued during the immediate postoperative period (Grade B), when epidural analgesia is not feasible or contra-indicated

Epidural analgesia

Continuous thoracic epidural anaesthesia and analgesia, at a level appropriate to the site of incision are recommended for routine use (Grade A)

A combination of strong opioid and local anaesthetic is recommended (Grade A) because of the increased analgesic efficacy of the combination compared with strong opioids alone

Not recommended:

Systemic analgesia

IV clonidine (Grade D) because it is associated with an increased risk of hypotension and bradycardia

Conventional NSAIDs (Grade B) because pre-operative administration of these agents can increase the risk of intra- and postoperative bleeding

Corticosteroids for analgesia (Grade A) because of procedure-specific evidence showing no significant benefit in reducing pain scores and concerns that they could affect anastomotic and wound integrity (but they may be used for reduction of PONV)

Gabapentin/pregabalin (Grade D) due to a lack of procedure-specific evidence

Continuous administration of IV lidocaine limited to the pre-/intra-operative period (Grade D) because of inconsistent and insufficient procedure-specific evidence

COX-2-selective inhibitors (Grade B) (only for patients who do not receive epidural anaesthesia)

Strong opioids (Grade B) (only for patients who do not receive epidural anaesthesia)

Continuous administration of pre-/intra-operative IV lidocaine if continued during the immediate postoperative period, when epidural analgesia is not feasible or contra-indicated (Grade B)

Epidural analgesia

Continuous thoracic epidural anaesthesia and analgesia, at a level appropriate to the site of incision are recommended for routine use (Grade A)

Combination of strong opioid and local anaesthetic is recommended (Grade A) based on procedure-specific evidence of their combined efficacy, in reducing postoperative pain and opioid use, compared with LA alone

Operative techniques

The decision concerning the type of operative technique or incision to use for colonic resection should be primarily based on factors other than the management of postoperative pain, e.g. malignancy versus benign disease operative risk factors of the patient, risk of wound infection, and availability of surgical expertise (Grade D)

Horizontal/curved (transverse) incision is recommended over a vertical incision for analgesic and other benefits if the operative conditions allow (Grade B). In addition, the horizontal/curved incision is preferred for its cosmetic benefits (Grade D)

Diathermy is recommended over the scalpel (Grade C)

Maintenance of normothermia is recommended for improved clinical outcomes, but it is not helpful for reducing postoperative pain (Grade A)

Not recommended:

Systemic analgesia

IV clonidine (Grade D) because it associated with an increased risk of hypotension, sedation and bradycardia

The decision concerning the type of operative technique or incision to use for colonic resection should be primarily based on factors other than the management of postoperative pain, e.g. malignancy versus benign disease; operative risk factors of the patient; risk of wound infection; and availability of surgical expertise (Grade D)

This algorithm for treating postoperative pain is based on the PROSPECT Recommendations and illustrates the different treatment pathways for patients with no contra-indications to epidurals, patients with contra-indications to epidurals, patients undergoing laparoscopic colonic resection, as well as describing the steps of the peri-operative pathway and therapies that apply to all patients. Therapies that are not recommended are also indicated.

• The most common reasons for exclusion were the lack of VAS postoperative pain scores (32 studies), and the lack of a defined subgroup of patients undergoing colonic resection (16 studies)

This website provides recommendations for open and laparoscopic colonic resection. Results from the open and laparoscopic colonic resection studies are dealt with separately, because of the different pain profiles associated with these approaches.

• A majority of the studies assessed the effect of analgesic interventions in open colonic resection with the exception of:

• In five of seven studies, laparoscopic colonic resection was superior to open colonic resection for reducing postoperative pain scores: at rest, during coughing and mobilisation at 6 h (all p<0.05; n=29) (Stage 1997; LoE 2); at rest at 48 h (p<0.01) and during coughing 24–72 h, (p<0.01; n=44) (Danelli 2002; LoE 2); at rest and on coughing within the first week (p<0.02; n=60) (Schwenk 1998; LoE 2) and on Day 1 in two studies (p=0.003; n=403; p<0.05, n=39) (Leung 2004; LoE 1, Liang 2002; LoE 2). One study reported that open colonic resection was superior to laparoscopic colonic resection for the reduction of VAS pain scores at rest and activity at day 1 (p<0.05; n=60), but not from days 2–30 (Basse 2005; LoE 1). Another study showed no significant difference between laparoscopic-assisted colectomy and open colectomy for pain distress scores from baseline to 2 days, 2 weeks and 2 months postoperatively (Weeks 2002; LoE 1)

• In two of three studies, hand-assisted laparoscopic colonic surgery was superior to open colonic surgery for reduction of postoperative pain scores: during the first postoperative week (p<0.001; n=81) (Chung 2007; LoE 1), and on Day 1 (p=0.03), Day 3 and Day 14 (p<0.001; n=60) (Kang 2004; LoE 2); the third study reported no significant difference in postoperative VAS pain scores at rest and during movement on Days 1, 2, 3 and 7, and at Week 4 (n=55) (Maartense 2004; LoE 1)

• In addition, a meta-analysis of randomized clinical trials (comprising of 2512 procedures from 12 trials) comparing the short-term outcomes of laparoscopic with those of open resection for colorectal cancer demonstrated that laparoscopic colonic resection is associated with lower morbidity, reduced pain and/or analgesic consumption, a faster recovery and a shorter hospital stay than open resection, without compromising oncological clearance (Abraham 2004; LoE 1)

Study quality assessments, levels of evidence and grades of recommendation

Recommendations are graded according to the overall level of evidence (LoE) on which the recommendations are based, which is determined by the quality and source of evidence: Levels of evidence and grades of recommendations in PROSPECT reviews (from 2006).

Transferable evidence of analgesic efficacy from comparable procedures, or evidence of other outcomes such as adverse effects, has been included to support the procedure-specific evidence where this is insufficient to formulate the recommendations.

Most of the transferable evidence for colonic resection was supplemented from major abdominal surgery and gynaecological procedures.

Quantitative analyses

Overall, few meta-analyses could be performed that used data from more than two studies. This is because there are a limited number of studies of homogeneous design that report similar outcome measures. Therefore, the majority of the procedure-specific evidence was assessed only qualitatively.

In certain circumstances, recommendations for a type of treatment cannot be made due to limited or conflicting evidence. Areas which have been identified as requiring further investigation in the future are as follows:

In this section, data are available from studies that assessed pre-operative analgesia versus pre-operative placebo, as well as those that examine the concept of pre-emptive – or preventive – analgesia, assessed pre-operative analgesia versus the same analgesia given postoperatively.

A previous systematic review of pre-emptive analgesia for postoperative pain relief in a variety of surgical procedures – such as orthopaedic, dental, gynaecological and abdominal – concluded that there is no benefit of pre-emptive over postoperative administration (Møiniche 2002). More recently, a meta-analysis of studies comparing pre-operative interventions with similar postoperative interventions in various procedures, found that pre-operative epidural analgesia was effective in reducing postoperative pain scores, but that pre-operative NSAIDs, local anaesthetic wound infiltration, NMDA antagonists and opioids did not improve postoperative analgesia (Ong 2005b).

Despite these findings, it is considered that analgesic medication needs to be initiated in time to ensure an adequate analgesic effect in the immediate postoperative period. This may necessitate administration prior to the postoperative period.

PROSPECT Recommendations

Pre-operative COX-2-selective inhibitors are recommended (Grade B) for colonic resection based on procedure-specific evidence that they have an analgesic effect postoperatively (LoE 2), only for patients who do not receive epidural analgesia (LoE 4)

It is recommended that the use of COX-2-selective inhibitors should depend upon assessment of individual patient risks (Grade B): cardiovascular morbidity (transferable evidence, LoE 1), renal function and hepatic function (transferable evidence, LoE 3), or actual or recent gastroduodenal ulcer history (LoE 4). In addition, the potential risk of anastomotic leakage needs to be considered (transferable evidence, LoE 3). Further observations are required regarding the potential risk of N

Clinical Practice

Rofecoxib has been withdrawn from the market, and marketing of valdecoxib has been suspended in most countries

There is no procedure-specific evidence that pre-operative administration of COX-2-selective inhibitors is more effective than postoperative administration

Transferable Evidence from Other Procedures - Study information

A pre-operative single bolus of parecoxib was superior to placebo for postoperative pain scores on sitting-up over 24 h (p=0.02), providing a mean decrease of 14 mm in VAS scores on a 100 mm scale in patients undergoing abdominal hysterectomy (n=36)

Randomised endoscopic trials in healthy volunteers have shown that COX-2-selective inhibitors are associated with a lower incidence of upper gastrointestinal ulceration compared with conventional NSAIDs for short-term use

Studies in healthy volunteers demonstrated that COX-2-selective inhibitors had no effect on platelet aggregation

A randomised clinical trial showed that the COX-2-selective inhibitor rofecoxib was associated with significantly less intra-operative blood loss than the conventional NSAID diclofenac in patients undergoing abdominal or vaginal hysterectomy or breast surgery

Clinical studies investigating the response to oral challenge with COX-2-selective inhibitors in patients with aspirin-induced asthma have demonstrated that COX-2-selective inhibitors do not have an effect on respiratory function

A study to assess the safety of the COX-2-selective inhibitors parecoxib and valdecoxib following noncardiac general surgery (including gastrointestinal, orthopaedic, gynaecological, urological, and thoracic surgeries) showed no difference in the incidence of cardiovascular thromboembolic events, renal dysfunction/failure, gastrointestinal ulcer complications, and surgical wound-healing complications, compared with placebo (n=1062)

A review concluded that COX-2-selective inhibitors were as effective as conventional NSAIDs for treatment of postoperative pain in various surgical models, and offer a number of other advantages including: reduced incidence of gastrointestinal ulceration, no inhibitory effect on platelet function (and thereby a reduced risk of blood loss) and no induction of bronchospasm in patients with aspirin-sensitive asthma

A meta-analysis that included data from 17 parecoxib and 15 valdecoxib placebo-controlled trials in non-cardiac surgery showed that there was no significant association between short-term treatment with parecoxib and/or valdecoxib and an increase in cardiovascular thromboembolic adverse events, compared with placebo (n=8511 overall)

A retrospective cohort study showed that the COX-2-selective inhibitors rofecoxib and celecoxib were associated with a lower risk of acute kidney infection than less-selective NSAIDs

A pre-operative single bolus of COX-2-selective inhibitor did not significantly reduce postoperative pain scores at rest compared with placebo within 0–24 h in two studies of patients undergoing abdominal hysterectomy (n=40; n=36)

Two meta-analyses comparing pre-incisional and post-incisional NSAIDs/COX-2-selective inhibitors have found no significant benefit of pre-incisional administration for reducing pain scores

Two clinical trials showed that in patients who had undergone CABG surgery COX-2-selective inhibitors (valdecoxib and parecoxib) were associated with a higher rate of serious cardiovascular thromboembolic events (including myocardial infarction) compared with placebo

Hypersensitivity reactions and serious skin reactions (e.g. toxic epidermal necrolysis, Stevens-Johnson syndrome, and erythema multiforme) can occur with all COX-2-selective inhibitors. Serious skin reactions have been reported in association with valdecoxib at a higher rate than with other COX-2-selective agents

Conventional NSAIDs and COX-2-selective inhibitors have been associated with an increased risk of transient hepatotoxicity. Cases of acute hepatic failure have also been reported. Elderly females, with autoimmune disease, and taking other potentially hepatotoxic drugs, may be most susceptible

Short-term use of COX-2-selective inhibitors or conventional NSAIDs can increase the risk of transient renal impairment, especially in patients with existing renal dysfunction, and both types of agent have been associated with cases of acute renal failure in high-risk patients

Although there is some concern COX-2-selective inhibitors may impair wound healing, evidence from animal and clinical studies is conflicting (

One study in patients undergoing fast-track colonic surgery found that postoperative analgesia with the COX-2-selective inhibitor celecoxib was associated with a higher risk of anastomotic leakage, compared with when celecoxib was not used

PROSPECT Recommendations

Pre-operative conventional NSAIDs are not recommended (Grade B) despite their analgesic efficacy, because pre-operative administration of these agents can increase the risk of intra- and postoperative bleeding (transferable evidence, LoE 1)

In addition, pre-operative conventional NSAIDs are not recommended, because there is evidence from other procedures that pre-operative administration of conventional NSAIDs is no more effective than postincisional administration for reducing pain scores (Grade B) (transferable evidence, LoE 1). In addition, the potential risk of anastomotic leakage needs to be considered (transferable evidence, LoE 3)

Conventional NSAIDs have proven analgesic efficacy in a variety of surgical procedures

A meta-analysis of randomised controlled trials performed to evaluate the risk of morphine-related adverse effects in patients treated with NSAIDs, demonstrated that NSAIDs decreased the incidence of nausea, vomiting and sedation, but not pruritus, urinary retention or respiratory depression

One randomised trial in patients undergoing transurethral prostatectomy showed that diclofenac did not affect total blood loss compared with placebo

Pre-operative rofecoxib was superior to naproxen for reducing the use of postoperative supplementary analgesics within 12–18 h (p<0.05), but there was no significant difference within 0–24 h in patients undergoing abdominal hysterectomy

Two meta-analyses comparing pre-incisional and post-incisional NSAIDs/COX-2-selective inhibitors have found no significant benefit of pre-incisional administration for reducing pain scores

Two of three studies showed no significant difference between single bolus conventional NSAIDs administered before or after incision for postoperative pain scores in patients undergoing abdominal hysterectomy Nakayama et al 2001aClick here for more information

Of three studies in abdominal hysterectomy, all showed no significant difference between pre-incisional and post-incisional conventional NSAIDs for supplementary analgesic consumption (n=65; n=30; n=77)

Post-incisional NSAID was superior to pre-incisional NSAID for extending the time to first analgesic request in one study (n=30)

Pre-incisional administration of conventional NSAIDs conferred no significant benefit over post-incisional administration for reducing the incidence of PONV in two studies of patients undergoing abdominal hysterectomy (n=65, n=30)

Randomised endoscopic trials in healthy volunteers have shown that COX-2-selective inhibitors are associated with a lower incidence of upper gastrointestinal ulceration compared with conventional NSAIDs for short-term use

Conventional NSAIDs and COX-2-selective inhibitors have been associated with an increased risk of transient hepatotoxicity. Cases of acute hepatic failure have also been reported. Elderly females, with autoimmune disease, and taking other potentially hepatotoxic drugs, may be most susceptible

Short-term use of conventional NSAIDs or COX-2-selective inhibitors can increase the risk of transient renal impairment, especially in patients with existing renal dysfunction, and both types of agent have been associated with cases of acute renal failure in high-risk patients

PROSPECT Recommendations

Pre-operative corticosteroids are not recommended for analgesia (Grade A) because of procedure-specific evidence showing no significant benefit in reducing VAS pain scores (LoE 1) and concerns that they could affect anastomotic and wound integrity (LoE 4). However, they may be used for reduction of PONV (transferable evidence, LoE 1)

Clinical Practice

Nausea and vomiting are frequent in abdominal surgeries, and corticosteroids may be used for their anti-emetic effects in patients at risk

A single pre-operative high-dose bolus of corticosteroid may be considered in high-risk pulmonary patients

Corticosteroids are not used in routine clinical practice because of the concerns that they could affect anastomotic and wound integrity

Transferable Evidence from Other Procedures - Study information

A single prophylactic dose of corticosteroid is effective for preventing PONV in surgery associated with high emetic effects

A review of major abdominal surgery, a randomised study of patients at high-risk of nausea and vomiting undergoing surgery, and a systematic review of drugs that prevent PONV, all showed that corticosteroids decrease PONV

A meta-analysis showed that a single pre-operative dose of IV methylprednisolone (15–30 mg/kg) was associated with significantly fewer pulmonary complications compared with placebo or no treatment, but data on postoperative pain could not be meta-analysed Sauerland et al 2000Click here for more information

IV methylprednisolone (30 mg/kg) significantly decreased pulmonary complications compared with placebo in one study identified in a review of major abdominal surgery

Corticosteroids did not significantly decrease pain compared with placebo in two studies identified in a review of major abdominal surgery

PROSPECT Recommendations

Gabapentin/pregabalin cannot be recommended at this time (Grade D, LoE 4) due to a lack of procedure-specific evidence, although analgesic data from other procedures are promising

Clinical Practice

[None cited]

Transferable Evidence from Other Procedures

Four systematic reviews and a meta-analysis evaluated the use of gabapentinoids for postoperative analgesia and demonstrated significant reductions in postoperative pain and supplementary analgesic requirements compared with inactive controls

Open Colonic Resection-Specific Evidence

PROSPECT Recommendations

Continuous administration of IV lidocaine limited to the pre-/intra-operative period is not recommended (Grade D, LoE 4) because of inconsistent and insufficient procedure-specific evidence (LoE 1)

Continuous administration of pre/intra-operative IV lidocaine is recommended if continued during the immediate postoperative period, when epidural analgesia is not feasible or contra-indicated (Grade B), based on transferable evidence (LoE 1) and limited procedure-specific evidence (LoE 2) for recovery benefits, compared with control (see Intra-operative and Postoperative IV lidocaine sections)

Clinical Practice

IV lidocaine can be considered as an alternative when there are contra-indications to epidural analgesia techniques

Further evidence is needed to precisely define the role of IV lidocaine in this setting, including direct comparisons with epidural analgesia

IV lidocaine may induce hypotension

If IV lidocaine is used it is recommended that safety data are taken into account

PROSPECT Recommendations

Clinical Practice

There is a lack of clinical experience with NMDA receptor antagonists. Moreover, NMDA receptor antagonists are associated with adverse events, e.g. ketamine is known for its increased risk of CNS side effects

Transferable Evidence from Other Procedures

Studies of intravenous or neuraxial ketamine in a variety of surgeries, including abdominal, gynaecological, orthopaedic, gastric, hepatic, and genitourinary surgery, showed a reduction in postoperative pain and opioid use when used as an adjunct to morphine

In patients undergoing laparoscopic cholecystectomy, dextromethorphan (pre- incisional and post gallbladder removal) was superior to control for reducing VAS scores, reducing the use of supplementary analgesics, and increasing the time to first analgesic request

Low-dose ketamine was associated with few and mild adverse effects, especially when administered in conjunction with general anaesthesia

A systematic review found that dextromethorphan did not reduce postoperative pain scores with a clinically significant magnitude, and although significant decreases in supplemental opioid consumption were observed, these were of questionable clinical importance in most cases

Two meta-analyses comparing pre-incisional and postincisional treatments found no significant analgesic benefit of pre-incisional administration of NMDA receptor antagonists

Open Colonic Resection-Specific Evidence - Study information

IM dextromethorphan was superior to control for reducing postoperative pain scores during coughing at 1, 2, 4, 8 and 24 h (p<0.001; n=60), although there were no significant differences in resting pain scores between the groups at any time point assessed

IM dextromethorphan significantly reduced the time to passage of first flatus, compared with the control (p<0.0001; n=60)

IV magnesium provided no significant benefit over placebo for reducing the following postoperative outcomes: pain scores at rest or during movement; morphine requirements for 0–24 h; sedation scores 0–48 h; incidence of nausea and vomiting; time to first bowel movement; and time to first flatus (n=47)

The incidence of morphine-related side-effects (drowsiness, dizziness, nausea, vomiting and pruritus) was similar in both the IM dextromethorphan and control groups (n=60)

Dextromethorphan conferred no significant benefit over control for reducing the length of hospital stay (n=60)

PROSPECT Recommendations

Pre-operative administration of strong opioids is not recommended (Grade B) for colonic resection as they are significantly less effective than postoperative strong opioids for reducing postoperative pain (transferable evidence, LoE 1)

Pre-incisional strong opioids provided no significant benefit over post-incisional strong opioids for increasing the time to first analgesic request in three studies of patients undergoing abdominal hysterectomy reporting this parameter (n=34, n=85, n=39)

A meta-analysis of studies comparing pre-operative interventions with similar postoperative interventions in various procedures found that pre-operative NSAIDs and local anaesthetic wound infiltration improved analgesic consumption and time to first rescue analgesic request, but not pain scores. Evidence did not support an improvement in postoperative analgesia following administration of pre-operative NMDA antagonists and opioids

Pre-incisional strong opioids were associated with a similar incidence of PONV to post-incisional strong opioids in patients undergoing abdominal hysterectomy (n=34, n=40, n=60)

Open Colonic Resection-Specific Evidence

PROSPECT Recommendations

Pre-operative administration of weak opioids is not recommended (Grade B) based on procedure-specific evidence that it has limited postoperative analgesic benefit compared with postoperative administration (LoE 2)

Clinical Practice

Tramadol 300 mg is considered to be a clinically effective dose, and therefore the 100 mg dose used in the study by Wordliczek et al. is probably too low to provide sufficient pain relief

Transferable Evidence from Other Procedures

A systematic review of pre-emptive analgesia for postoperative pain relief in a variety of surgical procedures – such as orthopaedic, dental, gynaecological and abdominal – has concluded that there is no benefit of pre-emptive over postoperative administration

A meta-analysis of studies comparing pre-operative interventions with similar postoperative interventions in various procedures found that pre-operative NSAIDs and local anaesthetic wound infiltration improved analgesic consumption and time to first rescue analgesic request, but not pain scores. Evidence did not support an improvement in postoperative analgesia following administration of pre-operative NMDA antagonists and opioids

Open Colonic Resection-Specific Evidence - Study information

Pre-operative administration of IV tramadol was superior to administration immediately after peritoneal closure or postoperatively for reducing total tramadol consumption (p<0.05; n=90)

Pre-operative administration of IV tramadol resulted in a significantly shorter time to first analgesic request compared with administration immediately after peritoneal closure, or immediately following surgery (p<0.01; n=90)

Tramadol 100 mg administered pre- or intra-operatively, did not confer any benefit for reducing the incidence of PONV compared with postoperative IV tramadol 100 mg (n=90)

PROSPECT Recommendations

Continuous thoracic epidural anaesthesia and analgesia at a level appropriate to the site of incision are recommended for routine use (Grade A), based on superior postoperative analgesic and safety benefits compared with systemic techniques (procedure-specific evidence, LoE 1, also see Intra-operative and Postoperative Epidural Analgesia sections), except in a minority of patients with a contra-indication to epidural administration

Pre-operative administration of a single-shot epidural analgesia produces a similar postoperative analgesic efficacy to postoperative administration

Where epidural techniques are used, it is recommended that a combination of strong opioid and local anaesthetic is used (Grade A) because of the increased analgesic efficacy of the combination compared with strong opioids alone and to reduce the dose of strong opioid and its associated side-effects (procedure-specific evidence, LoE 1, see Intra-operative and Postoperative Epidural Analgesia sections)

Where epidural techniques are used, it is recommended that the epidural catheter is inserted pre-operatively because this is the most practical timing for insertion (Grade D, LoE 4)

Clinical Practice

In colonic surgery, the analgesic and recovery benefits of an epidural outweigh the risks of rare major complications and warrant the use of this more labour-intensive treatment

Where epidural techniques are used, the most practical timing for insertion of the epidural catheter is pre-operatively

1 mg epidural morphine is considered inadequate to block visceral pain; however, larger doses are likely to cause bladder dysfunction. Therefore, pre-operative epidural administration of local anaesthetic with opioids is preferred to opioids alone

Transferable Evidence from Other Procedures - Study information

Pre-operative epidural morphine bolus was superior to epidural saline placebo for reducing postoperative pain scores at rest and on movement at 1 and 6 h (p<0.05 for all comparisons; n=36) in patients undergoing abdominal hysterectomy

Incidence of postoperative nausea and vomiting was similar between the pre-operative spinal morphine group and the pre-operative spinal morphine + sufentanil group (n=77)

Spinal bupivacaine conferred no significant benefit over placebo for reducing VAS pain scores at rest, mobilisation or during coughing at any of the time points assessed (2, 6 and 12 h, Days 1, 2 and 3) (n=40)

Spinal clonidine conferred no significant benefit over spinal bupivacaine for reducing VAS pain scores at rest, mobilisation or during coughing at any of the time points assessed (2, 6 and 12 h, Days 1, 2 and 3) (n=40)

PROSPECT Recommendations

Bilateral TAP block is not recommended at the current time (Grade D, LoE 4) because of limited procedure-specific evidence, despite some positive transferable evidence (LoE 1)

Clinical Practice

The single-shot TAP block technique may provide effective postoperative analgesia but the duration is limited. Despite this, further study evidence is expected which may support the use of this technique

Pre-operative bilateral TAP block significantly reduced postoperative sedation scores, compared with control, at 4 and 6 h postoperatively (p=0.01), although there was no significant difference between the groups at 2 and 24 h, or in the PACU

Pre-operative bilateral TAP block was associated with a significantly higher incidence of PONV, compared with control (p<0.05)

Relaxation tapes provided no significant benefit over routine postoperative care for the reduction of VAS pain scores at rest or coughing during postoperative Days 1–4 (n=40)

There was no significant difference in the total analgesic consumption or the number of analgesic requests between patients in the relaxation and guided imagery groups (n=42)

Time to first flatus and first bowel movement was similar for patients in the guided imagery and relaxation groups (n=42)

Time to first flatus and first bowel movement was similar for patients in the relaxation and routine care groups (n=42)

One study found that care by guided imagery provided no benefit over routine postoperative care for reducing the median length of hospital stay, postoperative ileus or the incidence of nausea or vomiting (n=130)

Open Colonic Resection-Specific Evidence - Study information

PROSPECT Recommendations

Pre-operative pentoxifylline is not recommended (Grade D, LoE 4) due to limited procedure-specific evidence of its analgesic effect

Clinical Practice

Further studies are needed to recommend the use of pentoxifylline in clinical practice

Transferable Evidence from Other Procedures

[None Cited]

Open Colonic Resection-Specific Evidence - Study information

Pre-operative IV pentoxifylline was superior to placebo for the reduction of VAS pain scores during coughing after 1, 2, and 4 h, and on Days 1 and 2 (p<0.05; n=40), however, there was no siginificant difference between the groups for resting pain scores at each of the time points assessed (1, 2, 4 h and Days 1, 2 and 3)

Pre-operative IV pentoxifylline was superior to placebo for reducing morphine consumption during Days 1–3 (p<0.0001; n=40)

Pre-operative IV pentoxifylline was superior to placebo for extending the time until first PCA morphine trigger (p<0.0001; n=40)

Pre-operative IV pentoxifylline was superior to placebo for reducing the time until first flatus

PROSPECT Recommendations

Intra-operative COX-2-selective inhibitors are recommended (Grade B) for colonic resection based on procedure-specific evidence that they have an analgesic effect postoperatively (LoE 2), only for patients who do not receive epidural analgesia (LoE 4)

It is recommended that the use of COX-2-selective inhibitors should depend upon assessment of individual patient risks (Grade B) (cardiovascular morbidity [transferable evidence, LoE 1], renal function and hepatic function [transferable evidence, LoE 3], or actual or recent gastroduodenal ulcer history [LoE 4]). In addition, the potential risk of anastomotic leakage needs to be considered (transferable evidence, LoE 3). Further observations are required regarding the potential risk of NSAIDs and

Clinical Practice

Rofecoxib has been withdrawn from the market, and marketing of valdecoxib has been suspended in most countries

There is no procedure-specific evidence that intra-operative administration of COX-2-selective inhibitors is more effective than postoperative administration

Transferable Evidence from Other Procedures - Study information

Randomised endoscopic trials in healthy volunteers have shown that COX-2-selective inhibitors are associated with a lower incidence of upper gastrointestinal ulceration compared with conventional NSAIDs for short-term use

Studies in healthy volunteers demonstrated that COX-2-selective inhibitors had no effect on platelet aggregation

A randomised clinical trial showed that the COX-2-selective inhibitor rofecoxib was associated with significantly less intra-operative blood loss than the conventional NSAID diclofenac in patients undergoing abdominal or vaginal hysterectomy or breast surgery

Clinical studies investigating the response to oral challenge with COX-2-selective inhibitors in patients with aspirin-induced asthma have demonstrated that COX-2-selective inhibitors do not have an effect on respiratory function

A study to assess the safety of the COX-2-selective inhibitors parecoxib and valdecoxib following noncardiac general surgery (including gastrointestinal, orthopaedic, gynaecological, urological, and thoracic surgeries) showed no difference in the incidence of cardiovascular thromboembolic events, renal dysfunction/failure, gastrointestinal ulcer complications, and surgical wound-healing complications, compared with placebo (n=1062)

A review concluded that COX-2-selective inhibitors were as effective as conventional NSAIDs for treatment of postoperative pain in various surgical models, and offer a number of other advantages including: reduced incidence of gastrointestinal ulceration, no inhibitory effect on platelet function (and thereby a reduced risk of blood loss) and no induction of bronchospasm in patients with aspirin-sensitive asthma

A meta-analysis that included data from 17 parecoxib and 15 valdecoxib placebo-controlled trials in non-cardiac surgery showed that there was no significant association between short-term treatment with parecoxib and/or valdecoxib and an increase in cardiovascular thromboembolic adverse events, compared with placebo (n=8511 overall)

A retrospective cohort study showed that the COX-2-selective inhibitors rofecoxib and celecoxib were associated with a lower risk of acute kidney infection than less-selective NSAIDs

A pre-operative single bolus of COX-2-selective inhibitor did not significantly reduce postoperative pain scores at rest compared with placebo within 0–24 h in two studies of patients undergoing abdominal hysterectomy (n=40; n=36)

Two clinical trials showed that in patients who had undergone CABG surgery COX-2-selective inhibitors (valdecoxib and parecoxib) were associated with a higher rate of serious cardiovascular thromboembolic events (including myocardial infarction) compared with placebo

Hypersensitivity reactions and serious skin reactions (e.g. toxic epidermal necrolysis, Stevens-Johnson syndrome, and erythema multiforme) can occur with all COX-2-selective inhibitors. Serious skin reactions have been reported in association with valdecoxib at a higher rate than with other COX-2-selective agents

Conventional NSAIDs and COX-2-selective inhibitors have been associated with an increased risk of transient hepatotoxicity. Cases of acute hepatic failure have also been reported. Elderly females, with autoimmune disease, and taking other potentially hepatotoxic drugs, may be most susceptible

Short-term use of COX-2-selective inhibitors or conventional NSAIDs can increase the risk of transient renal impairment, especially in patients with existing renal dysfunction, and both types of agent have been associated with cases of acute renal failure in high-risk patients

Although there is some concern COX-2-selective inhibitors may impair wound healing, evidence from animal and clinical studies is conflicting

One study in patients undergoing fast-track colonic surgery found that postoperative analgesia with the COX-2-selective inhibitor celecoxib was associated with a higher risk of anastomotic leakage, compared with when celecoxib was not used

Open Colonic Resection-Specific Evidence - Study information

Intra-operative IV parecoxib (40 mg) conferred some benefit over placebo for the reduction of postoperative resting pain scores Click here for more information

There were no significant differences between the intra-operative IV parecoxib and pre-operative IV parecoxib groups for NRS pain scores at rest, or during coughing, during the first 48 h postoperatively

PROSPECT Recommendations

Clonidine is not recommended (Grade D), despite limited procedure-specific evidence for analgesic efficacy, because it is associated with an increased risk of hypotension, sedation and bradycardia (LoE 4)

Clinical Practice

The risk/benefit ratio for clonidine is unclear. Recognised side effects include hypotension, sedation, dizziness and bradycardia

There is no consensus among clinicians on the optimum dose of clonidine that should be used

Oral nifedipine was significantly inferior to placebo for postoperative pain scores at rest at 16 and 24 h (p<0.05; n=46)

Nimodipine or nifedipine provided no significant benefit over placebo for reducing the following postoperative outcomes: morphine requirements for 0–24 h; sedation scores for 0–48 h; the incidence of nausea and vomiting; time to first bowel movement and time to first flatus (n=69)

PROSPECT Recommendations

Gabapentin/pregabalin cannot be recommended at this time (Grade D, LoE 4) due to a lack of procedure-specific evidence, although analgesic data from other procedures are promising

Clinical Practice

[None cited]

Transferable Evidence from Other Procedures

Four systematic reviews and a meta-analysis evaluated the use of gabapentinoids for postoperative analgesia and demonstrated significant reductions in postoperative pain and supplementary analgesic requirements compared with inactive controls

Open Colonic Resection-Specific Evidence

PROSPECT Recommendations

Continuous administration of IV lidocaine limited to the pre/intra-operative period is not recommended (Grade D) because of inconsistent and insufficient procedure-specific evidence

Continuous administration of pre/intra-operative IV lidocaine continuous administration is recommended if continued during the immediate postoperative period when epidural analgesia is not feasible or contra-indicated (Grade B), based on transferable evidence (LoE 1) and limited procedure-specific evidence (LoE 2) for recovery benefits compared with control

Clinical Practice

IV lidocaine can be considered as an alternative when there are contra-indications to epidural analgesia techniques

Further evidence is needed to precisely define the role of IV lidocaine in this setting, including direct comparisons with epidural analgesia

IV lidocaine may induce hypotension

If IV lidocaine is used it is recommended that safety data are taken into account

Transferable Evidence from Other Procedures - Study information

A meta-analysis of randomised clinical trials performed to evaluate the effect of continuous IV lidocaine infusion during and after abdominal surgery reported that lidocaine significantly reduced postoperative VAS pain scores, duration of postoperative ileus, incidence of PONV, and length of hospital stay, compared with the controls

PROSPECT Recommendations

Clinical Practice

There is a lack of clinical experience with NMDA receptor antagonists. Moreover, NMDA receptor antagonists are associated with adverse events, e.g. ketamine is known for its increased risk of CNS side effects

Transferable Evidence from Other Procedures

Studies of intravenous or neuraxial ketamine in a variety of surgeries, including abdominal, gynaecological, orthopaedic, gastric, hepatic, and genitourinary surgery, showed a reduction in postoperative pain and opioid use when used as an adjunct to morphine

In patients undergoing laparoscopic cholecystectomy, dextromethorphan (pre- incisional and post gallbladder removal) was superior to control for reducing VAS scores, reducing the use of supplementary analgesics, and increasing the time to first analgesic request

Low-dose ketamine was associated with few and mild adverse effects, especially when administered in conjunction with general anaesthesia

A systematic review found that dextromethorphan did not reduce postoperative pain scores with a clinically significant magnitude, and although significant decreases in supplemental opioid consumption were observed, these were of questionable clinical importance in most cases

Two meta-analyses comparing pre-incisional and postincisional treatments found no significant analgesic benefit of pre-incisional administration of NMDA receptor antagonists

Open Colonic Resection-Specific Evidence - Study information

Intra-operative ketamine was superior to placebo for reducing postoperative pain scores in the first 15 min (p<0.05), decreasing morphine use for 0–24 h compared with placebo (p<0.01), and extending the time to first analgesic request (p<0.001) compared with placebo (n=50)

IV magnesium provided no significant benefit over placebo for reducing the following postoperative outcomes: pain scores at rest or during movement; morphine requirements for 0–24 h; sedation scores 0–48 h; incidence of nausea and vomiting; time to first bowel movement; and time to first flatus (n=47)

However, in patients not indicated for epidural anaesthesia, systemic intra-operative strong opioids are recommended to provide early postoperative pain relief (Grade B), based on transferable evidence (LoE 1) of analgesic efficacy

Clinical Practice

[None Cited]

Transferable Evidence from Other Procedures - Study information

Intra-operative strong opioid provided a benefit over placebo up to 4 h for reducing postoperative pain scores at rest (one of three studies) and reducing the supplementary analgesic consumption (three studies), but showed no significant difference for the time to first analgesic request (one study), in patients undergoing hysterectomy Click here for more information

Low-dose remifentanil infusion plus titrated desflurane had a similar time to first request of supplementary analgesia and a similar incidence of PONV compared with a high-dose remifentanil infusion plus fixed-dose desflurane (n=49)

Sufentanil anaesthesia was superior to remifentanil anaesthesia plus intra-operative bolus IV morphine for reducing postoperative pain scores at 2 h, but the scores were similar from 2–12 h (p<0.01; n=30)

Sufentanil anaesthesia was superior to remifentanil anaesthesia plus intra-operative bolus IV morphine for the reduction of supplementary analgesic consumption in the PACU and at 4, 12 and 24 h (p<0.05; n=30)

Sufentanil anaesthesia was superior to remifentanil anaesthesia plus intra-operative bolus IV morphine for extending the time to first analgesic request (p<0.05; n=30)

Sufentanil anaesthesia was similar to remifentanil anaesthesia plus intra-operative bolus IV morphine for the incidence of PONV and sedation scores (n=30)

Remifentanil infusion at a low-dose compared with remifentanil infusion at a high-dose was associated with a similar percentage of sedated patients Click here for more information

Clinical Practice

Tramadol 300 mg is considered to be a clinically effective dose, and therefore the 100 mg dose used in the study by Wordliczek et al. is likely to be too low to provide sufficient pain relief

Transferable Evidence from Other Procedures - Study information

Intra-operative IV tramadol was superior to placebo for reducing tramadol use and postoperative pain scores in the PACU following abdominal surgery (p<0.05 for all comparisons; n=60)

Intra-operative IV tramadol was superior to placebo for reducing the incidence (p<0.05) and severity (p<0.05) of PONV following abdominal surgery (n=60)

For patients undergoing laparoscopic cholecystectomy, intra-operative tramadol IV at wound closure was superior to control for reducing VAS scores, reducing the use of supplementary analgesics and increasing the time to first analgesic request

Intra-operative IV tramadol was similar to placebo for the number of postoperative PCA boluses delivered and total tramadol consumption (n=60)

Open Colonic Resection-Specific Evidence - Study information

Administration of IV tramadol immediately after peritoneal closure, or immediately following surgery extended the time to first analgesic request compared with pre-operative administration (p<0.01; n=90)

PROSPECT Recommendations

Continuous thoracic epidural anaesthesia and analgesia is recommended (Grade A) for routine use in colonic resection based on its benefit in reducing postoperative pain, systemic opioid use and bowel recovery time (procedure-specific evidence, LoE 1)

A combination of epidural local anaesthetic (LA) and strong opioid is recommended for epidural analgesia (Grade A), based on procedure-specific evidence of their combined efficacy in reducing postoperative pain and systemic opioid use, compared with LA alone (LoE 1). However, the addition of opioid to epidural LA results in an increase in time to first bowel movement (LoE 1)

Addition of clonidine to the combination of epidural LA + opioid is not recommended (Grade D) because of side effects, despite favourable effects on pain scores

Clinical Practice

Thoracic epidural is considered to be more appropriate than lumbar epidural for anaesthesia and analgesia in colonic resection

Epidural analgesia is associated with a relatively high degree of patient monitoring and rare major complications

A minority of patients may need to receive general anaesthesia plus systemic analgesia due to a contra-indication to the epidural technique

Two studies demonstrated that epidural bupivacaine conferred a benefit over general anaesthesia and systemic analgesia for reducing postoperative pain scores at rest for 1–72 h in one study (all p<0.05; n=116)

Epidural bupivacaine had a similar incidence of nausea compared with GA and IV plus postoperative PCA morphine (n=26)

A meta-analysis of randomised studies performed to compare the effect of local anaesthetic epidural analgesia with parenteral opioid analgesia in patients undergoing colorectal surgery, found no significant difference in the incidence of PONV (5 studies analysed; n=189), anastomotic leakage (7 studies analysed; n=459), or length of hospital stay (n=716)

PROSPECT Recommendations

Spinal analgesia is not recommended in combination with epidural anaesthesia (Grade B), based on a lack of benefit in reducing postoperative pain in colonic resection (LoE 2). Moreover, it introduces a greater level of complexity (LoE 4)

PROSPECT Recommendations

No recommendation can be made about general anaesthetic techniques for open colonic resection because of limited procedure-specific evidence

Clinical Practice

For laparoscopic procedures, the use of nitrous oxide may result in increased bowel distension

Transferable Evidence from Other Procedures

One randomised study investigating the efficacy of prophylactic antimetic interventions in patients undergoing surgery with general anaesthesia concluded that the risk of PONV was 12% greater with N2O compared with nitrogen

One randomised study comparing nitrous oxide-based anaesthesia with nitrous oxide-free anaesthesia in patients undergoing major surgery, found that the avoidance of nitrous oxide decreased the incidence of postoperative complications, but did significantly reduce the length of hospital stay (Myles 2007)

One study reported that moderate-to-severe bowel distension was significantly less common in patients following GA with nitrogen, compared with nitrous oxide (p<0.001; n=344)

Nitrous oxide was superior to intra-operative IV remifentanil for the reduction of VAS pain scores on arrival in the PACU (p<0.05; n=60), but not after 5, 10 or 15 min

Two studies reported no significant difference in the level of PCA opioid consumption (piritramide) between patients receiving GA with nitrogen or nitrous oxide (n=344; n=408)

Two studies showed that the incidence of postoperative nausea and vomiting was similar with nitrous oxide and nitrogen (n=344; n=408)

There was no significant difference in the time to first flatus, first bowel movement, or first intake of solid food between patients in the groups receiving GA with nitrogen or nitrous oxide (n=408)

The length of hospital stay was similar for patients in the groups that received general anaesthesia with nitrogen and general anaesthesia with nitrous oxide (n=408)

There were no significant differences between the nitrous oxide and intra-operative IV remifentanil groups in VAS pain scores at rest or movement from 0–24 h postoperatively (n=60)

There was no significant difference between the nitrous oxide and intra-operative IV remifentanil groups for postoperative morphine consumption in the PACU, or during the first postoperative day (n=60)

There was a similar incidence of postoperative nausea and vomiting between patients receiving nitrous oxide and IV remifentanil (n=60)

PROSPECT Recommendations

The decision concerning the type of operative technique or incision to use for colonic resection should be primarily based on factors other than the management of postoperative pain, e.g. malignancy versus benign disease; operative risk factors of the patient; risk of wound infection; and availability of surgical expertise (Grade D, LoE 4)

See laparoscopic section for recommendations on pain management for laparoscopic colonic resection

A horizontal/curved (transverse) incision is recommended over a vertical incision for analgesic and other benefits, if the operative conditions allow (Grade B) based on limited procedure-specific evidence (LoE 2) and transferable evidence. In addition, the horizontal/curved incision is preferred for its cosmetic benefits (Grade D, LoE 4)

Diathermy is recommended over the scalpel (Grade B), based on analgesic benefits as well as greater speed of incision and less blood loss (transferable evidence, LoE 2)

Clinical Practice

The decision to employ a laparoscopic versus open approach for colonic surgery is based on multiple factors such as the indication for surgery (e.g. benign or malignant disease) and surgical expertise, as well as the desired outcomes

If the surgical indication allows, a transverse incision is preferred for abdominal procedures such as colonic resection

Transferable Evidence from Other Procedures

The transverse incision was similar to the vertical incision for access to intra-abdominal structures and resulted in significantly less postoperative pain and a lower incidence of pulmonary complications; however, vertical laparotomy is associated with a shorter operating time and better possibilities for extension of the incision, as found in a systematic review in abdominal surgery

Laparotomy incisions using diathermy had significantly lower VAS scores at 48 h (p<0.05), morphine consumption over the first 5 days (p<0.04), less blood loss (p=0.002), and were associated with a faster speed of incision (p<0.04) compared with scalpel incisions in patients undergoing elective midline laparotomy (n=100)

Laparoscopic surgery resulted in an increased operating time, but reduced postoperative pain, hospital stay and return to normal activity compared with open surgery, as demonstrated in a number of reviews of the literature of patients undergoing resection for colonic cancer, cholecystectomy, appendectomy (systematic) and groin hernia (systematic)

Open Colonic Resection-Specific Evidence - Study information

A transverse incision conferred significant benefit over a midline vertical incision for reducing postoperative pain on movement on Days 1 and 3, and reducing supplementary analgesic consumption (all p<0.05); however, both incision techniques were similar for postoperative pain scores at rest (n=40)

A transverse incision was similar to a midline vertical incision for the time to resume normal diet, time to first bowel movement and duration of hospital stay (n=40)

One study reported that there was no significant difference in the incidence of PONV between the laparoscopic colonic resection and open colonic resection techniques (n=60)

A meta-analysis of seven studies reporting analgesic outcomes showed a significant benefit of laparoscopic resection over open colonic resection for reduced pain at rest and on coughing, and reduced analgesic requirement for up to 3 days (not all studies recorded pain scores)

Meta-analysis of twelve studies showed that laparoscopic resection reduced morbidity, wound infection, time to recovery and hospital stay compared with open resection

A systematic review of laparoscopic resection of colon cancer, combined with expert opinion, concluded that pain is less severe and that less analgesia is required after laparoscopic resection than open resection

A systematic review comparing laparoscopic with open surgery for colorectal cancer, concluded that laparoscopic surgery was associated with less blood loss, less postoperative pain, less postoperative analgesic consumption, faster return to normal bowel function, and a shorter hospital stay

A systematic review comparing laparoscopic versus open total mesorectal excision for rectal cancer reported that one of two randomised controlled studies showed laparoscopic surgery was superior for reducing postoperative pain scores

Hand-assisted laparoscopic colectomy was superior to open colectomy for reducing the time to first flatus and first bowel movement Click here for more information

Two studies showed that hand-assisted laparoscopic colectomy was superior to open colectomy for reducing the length of hospital stay (p=0.004, n=81; p<0.001, n=60)

One study showed that hand-assisted laparoscopic colectomy was superior to open colectomy for reducing the time until first oral food intake (p<0.05, n=60)

A systematic review comparing laparoscopic versus open total mesorectal excision for rectal cancer reported that two of three randomised studies found no significant difference between laparoscopic and open techniques for reducing postoperative analgesic consumption. However, there was a trend for less analgesia in the laparoscopic group

Hand-assisted laparoscopic proctocolectomy conferred no significant benefit over open proctocolectomy for reducing VAS pain scores at rest and during movement on Days 1, 2, 3 and 7, and at Week 4 (n=55)

There was no significant difference in the postoperative morphine requirement between patients who received hand-assisted laparoscopic proctocolectomy versus open proctolectomy at 24, 48 or 72 h (n=55)

Hand-assisted laparoscopic proctocolectomy conferred no significant benefit over open proctolectomy for reducing the time taken for patients to return to normal fluid or food consumption (n=55)

PROSPECT Recommendations

Maintenance of normothermia is recommended (Grade A) for improved clinical outcomes (procedure-specific evidence, LoE 1) but it is not helpful for reducing postoperative pain (LoE 1)

Clinical Practice

Although there are no benefits for pain reduction, keeping patients normothermic has benefits for reducing oxygen consumption and decreasing myocardial work, which is important for elderly patients and those at risk of cardiac events

Transferable Evidence from Other Procedures - Study information

One study showed that aggressive warming was superior to conventional warming in total hip arthroplasty for reducing intra-operative and total blood loss (p=0.002), but no difference in postoperative blood loss was observed (n=150)

A randomized controlled trial in high-risk patients showed that maintenance of normothermia reduced the incidence of morbid cardiac events in the peri-operative period compared with routine thermal care (p=0.02, n=300)

Open Colonic Resection-Specific Evidence - Study information

Maintenance of normothermia was associated with higher comfort scores and a similar heart rate and blood pressure than maintenance of hypothermia in one study (n=74)

Maintenance of normothermia was associated with lower incidence of wound infections, fewer transfusions and quicker suture removal and hospital discharge compared with maintenance of hypothermia (p=0.01 for all outcomes) (n=200)

Patients kept normothermic were similar to patients kept hypothermic for postoperative pain scores in three studies (n=74, n=200, n=30)

PROSPECT Recommendations

COX-2-selective inhibitors are recommended (Grade B) based on limited procedure-specific evidence (LoE 2) and transferable evidence (LoE 1). They should be given in combination with strong opioids for high-intensity pain, or with weak opioids for moderate- or low-intensity pain (Grade D, LoE 4), only for patients who do not receive epidural analgesia or with cessation of epidural analgesia (Grade D, LoE 4)

COX-2-selective inhibitors may be preferred to conventional NSAIDs in the peri-operative setting, in patients who have an increased risk of bleeding, or who are at risk of gastroduodenal ulcer/erosion (Grade B, transferable evidence, LoE1) or who have NSAID-induced asthma (transferable, LoE 1)

Randomised endoscopic trials in healthy volunteers have shown that COX-2-selective inhibitors are associated with a lower incidence of upper gastrointestinal ulceration compared with conventional NSAIDs for short-term use

Studies in healthy volunteers demonstrated that COX-2-selective inhibitors had no effect on platelet aggregation

Clinical studies investigating the response to oral challenge with COX-2-selective inhibitors in patients with aspirin-induced asthma have demonstrated that COX-2-selective inhibitors do not have an effect on respiratory function

A study to assess the safety of the COX-2-selective inhibitors parecoxib and valdecoxib following noncardiac general surgery (including gastrointestinal, orthopaedic, gynaecological, urological, and thoracic surgeries) showed no difference in the incidence of cardiovascular thromboembolic events, renal dysfunction/failure, gastrointestinal ulcer complications, and surgical wound-healing complications, compared with placebo (n=1062)

A meta-analysis that included data from 17 parecoxib and 15 parecoxib placebo-controlled trials in non-cardiac surgery, showed that there was no significant association between short-term treatment with parecoxib and/or valdecoxib and an increase in cardiovascular thromboembolic adverse events, compared with placebo (n=8511 overall)

A retrospective cohort study showed that the COX-2-selective inhibitors rofecoxib and celecoxib were associated with a lower risk of acute kidney infection than less-selective NSAIDs

Two clinical trials showed that in patients who had undergone CABG surgery COX-2-selective inhibitors (valdecoxib and parecoxib) were associated with a higher rate of serious cardiovascular thromboembolic events (including myocardial infarction) compared with placebo

Hypersensitivity reactions and serious skin reactions (e.g. toxic epidermal necrolysis, Stevens-Johnson syndrome, and erythema multiforme) can occur with all COX-2-selective inhibitors. Serious skin reactions have been reported in association with valdecoxib at a higher rate than with other COX-2-selective agents

Conventional NSAIDs and COX-2-selective inhibitors have been associated with an increased risk of transient hepatotoxicity. Cases of acute hepatic failure have also been reported. Elderly females, with autoimmune disease, and taking other potentially hepatotoxic drugs, may be most susceptible

Short-term use of COX-2-selective inhibitors or conventional NSAIDs can increase the risk of transient renal impairment, especially in patients with existing renal dysfunction, and both types of agent have been associated with cases of acute renal failure in high-risk patients

Although there is some concern that COX-2-selective inhibitors may impair wound healing, evidence from animal and clinical studies is conflicting

One study in patients undergoing fast-track colonic surgery found that postoperative analgesia with the COX-2-selective inhibitor celecoxib was associated with a higher risk of anastomotic leakage, compared with when celecoxib was not used

PROSPECT Recommendations

Conventional NSAIDs are recommended (Grade A), for their analgesic and opioid-sparing effect (procedure-specific evidence, LoE 1). They should be given in combination with strong opioids for high-intensity pain, or with weak opioids for moderate- or low-intensity pain (Grade D, LoE 4), only for patients who do not receive epidural analgesia or with cessation of epidural analgesia (Grade D, LoE 4)

Conventional NSAIDs are not recommended in patients who have an increased risk of bleeding, or who are at risk of gastroduodenal ulcer/erosion (Grade B, transferable evidence, LoE 1)

Clinical Practice

[None cited]

Transferable Evidence from Other Procedures - Study information

Conventional NSAIDs have proven analgesic efficacy in a variety of surgical procedures

A meta-analysis of randomised controlled trials that was performed to evaluate the risk of morphine-related adverse effects in patients treated with NSAIDs demonstrated that NSAIDs decreased the incidence of nausea, vomiting and sedation, but not pruritus, urinary retention or respiratory depression

Six out of eight studies showed a significant benefit of postoperative conventional NSAIDs compared with placebo for reducing postoperative pain scores in patients undergoing hysterectomy Click here for more information

Conventional NSAIDs conferred a significant benefit over placebo for reducing supplementary analgesia requirements over 24 h or more in patients undergoing abdominal hysterectomy Click here for more information

Conventional NSAIDs were superior to placebo for reducing morphine consumption in abdominal surgery but did not consistently reduce pain scores in two studies in abdominal surgery Click here for more information

One randomised trial in patients undergoing transurethral prostatectomy showed that diclofenac did not affect total blood loss compared with placebo

Two of three studies showed no significant analgesic benefit of conventional NSAIDs plus epidural analgesia compared with epidural analgesia alone Click here for more information

Results were inconsistent for conventional NSAIDs compared with placebo for the time to first analgesic request following abdominal hysterectomy Click here for more information

Conventional NSAIDs and placebo were not significantly different for the incidence of PONV (all groups received background strong opioid) in patients undergoing abdominal surgery Click here for more information

Diclofenac 50 mg IM bolus pre-operatively then postoperatively at 4 and 10 h, plus epidural analgesia using bupivacaine 0.5% continually infused at 8 mL/h did not confer a benefit for extending the time to first analgesic request compared with epidural analgesia alone in patients undergoing abdominal hysterectomy (n=26)

Randomised endoscopic trials in healthy volunteers have shown that COX-2-selective inhibitors are associated with a lower incidence of upper gastrointestinal ulceration compared with conventional NSAIDs for short-term use

Meta-analyses of randomised, controlled trials showed that peri-operative conventional NSAIDs increased the risk of postoperative bleeding requiring treatment and/or the risk of re-operation for haemostasis after tonsillectomy compared with controls

A randomised trial in healthy volunteers showed that three conventional NSAIDs (diclofenac, ketorolac and ketoprofen) caused a reversible platelet dysfunction

A randomised controlled trial showed that three conventional NSAIDs (diclofenac, ketorolac and ketoprofen) were associated with a similar incidence of surgical site bleeding after elective surgery

Aspirin and conventional NSAIDs can induce asthma attacks in patients with aspirin-exacerbated respiratory disease. Aspirin-induced asthma occurs in approximately 4–10% of the adult asthmatic population

Conventional NSAIDs and COX-2-selective inhibitors have been associated with an increased risk of transient hepatotoxicity. Cases of acute hepatic failure have also been reported. Elderly females, with autoimmune disease, and taking other potentially hepatotoxic drugs, may be most susceptible

Short-term use of conventional NSAIDs or COX-2-selective inhibitors can increase the risk of transient renal impairment, especially in patients with existing renal dysfunction, and both types of agent have been associated with cases of acute renal failure in high-risk patients

IM ketorolac (PRN) was superior to IM morphine (PCA or PRN) for reducing the time to first flatus (p<0.05) and length of hospital stay (dosing regimens not clear) (p<0.01; n=90)

IM ketorolac was superior to IM ketorolac plus IM or IV morphine on demand for reducing the length of time taken to recover from postoperative ileus (2.3 ± 0.5 days versus 4.2 ± 0.6 days; p<0.05; n=14)

IV PCA morphine + ketorolac was superior to IV PCA morphine alone for reducing total morphine consumption (p<0.05; n=74); however there was no significant difference between the groups for the duration of IV PCA morphine use

The incidence of postoperative nausea and vomiting was similar in the pre-operative + postoperative flurbiprofen axetil and placebo groups (n=40)

IM ketorolac plus PCA morphine conferred no significant benefit over PCA morphine alone for reducing postoperative pain scores, time to first flatus, time to first bowel movement and tolerance to liquids and regular diet (n=30)

There were no significant differences between the groups receiving IV PCA morphine or IV PCA morphine + ketorolac for VAS pain scores at rest or movement during postoperative Days 1–3 (n=74)

IV PCA morphine + ketorolac conferred no significant benefit over IV PCA morphine alone for reducing the time to first flatus (n=74)

The incidence of morphine-related side-effects (pruritus, nausea and vomiting and dizziness) was similar in the groups receiving IV PCA morphine + ketorolac or IV PCA morphine alone (n=74)

IV PCA morphine + ketorolac and IV PCA morphine alone were associated with a similar length of hospital stay (n=74)

PROSPECT Recommendations

Gabapentin/pregabalin cannot be recommended at this time (Grade D, LoE 4) due to a lack of procedure-specific evidence, although analgesic data from other procedures are promising

Clinical Practice

[None cited]

Transferable Evidence from Other Procedures

Four systematic reviews and a meta-analysis evaluated the use of gabapentinoids for postoperative analgesia and demonstrated significant reductions in postoperative pain and supplementary analgesic requirements compared with inactive controls

Open Colonic Resection-Specific Evidence

PROSPECT Recommendations

Postoperative IV lidocaine is recommended (Grade D, LoE 4) for open colonic resection when epidural analgesia is not feasible or contra-indicated (Grade B) based on transferable evidence (LoE 1) and limited procedure-specific evidence (LoE 2) for recovery benefits compared with control

Clinical Practice

IV lidocaine can be considered as an alternative when there are contra-indications to epidural analgesia techniques

If IV lidocaine is used it is recommended that safety data be taken into account

IV lidocaine may induce hypotension

Further evidence is needed to precisely define the role of IV lidocaine in this setting, including direct comparisons with epidural analgesia

Transferable Evidence from Other Procedures

A meta-analysis of randomised clinical trials performed to evaluate the effect of continuous IV lidocaine infusion during and after abdominal surgery reported that lidocaine significantly reduced postoperative VAS pain scores, duration of postoperative ileus, incidence of PONV, and length of hospital stay, compared with the controls

Open Colonic Resection-Specific Evidence - Study information

Peri-operative IV lidocaine significantly reduced the time to first flatus compared with the control group (p<0.05; n=60)

The time to first bowel movement was significantly shorter with peri-operative IV lidocaine compared with the control (p<0.05; n=60)

Peri-operative IV lidocaine significantly reduced the time taken to solid food intake compared with the control (p<0.001; n=60)

PROSPECT Recommendations

Clinical Practice

The maximum dose of ketamine that should be given to avoid side effects is 0.5 mg/kg

Clinical experience with NMDA receptor antagonists is lacking. Moreover, NMDA receptor antagonists are associated with adverse events, e.g. ketamine is known for its increased risk of CNS side effects

Transferable Evidence from Other Procedures

Studies of intravenous or neuraxial ketamine in a variety of surgeries, including abdominal, gynaecological, orthopaedic, gastric, hepatic, and genitourinary surgery, showed a reduction in postoperative pain and opioid use when used as an adjunct to morphine

In patients undergoing laparoscopic cholecystectomy, dextromethorphan (pre- incisional and post gallbladder removal) was superior to control for reducing VAS scores, reducing the use of supplementary analgesics, and increasing the time to first analgesic request

Low-dose ketamine was associated with few and mild adverse effects, especially when administered in conjunction with general anaesthesia

A systematic review found that dextromethorphan did not reduce postoperative pain scores with a clinically significant magnitude, and although significant decreases in supplemental opioid consumption were observed, these were of questionable clinical importance in most cases

Open Colonic Resection-Specific Evidence - Study information

IV magnesium provided no significant benefit over placebo for reducing the following postoperative outcomes: pain scores at rest or during movement; morphine requirements for 0–24 h; sedation scores 0–48 h; incidence of nausea and vomiting; time to first bowel movement; and time to first flatus (n=47)

PROSPECT Recommendations

Systemic strong opioids are recommended (Grade B) following colonic resection, based on transferable evidence for their efficacy in reducing high-intensity postoperative pain (VAS =50 mm) (LoE 1), with the following considerations:

In patients receiving epidural anaesthesia, epidural strong opioids are recommended 2–3 days postoperatively; after the catheter has been removed, systemic strong opioids can be administered for analgesia (Grade D, LoE 4)

Systemic strong opioids should only be used in combination with conventional NSAIDs or COX-2-selective inhibitors and paracetamol to reduce opioid use and its associated side-effects (Grade D, LoE 4)

Even though IV PCA strong opioids showed no analgesic benefit over IM PRN opioids in procedure-specific evidence (LoE 1), they are recommended (Grade B) based on greater patient satisfaction compared with regular (fixed-interval) or PRN dosing (transferable evidence, LoE 1); however, fixed-interval IV administration titrated to pain intensity is also recognised as an effective mode of administration (LoE 4)

IM strong opioids are not recommended because of the pain associated with these injections (Grade D, LoE 4)

Clinical Practice

Strong opioids are not associated with a ceiling effect, and thus can provide effective analgesia for most types of surgical procedures

Strong opioids may be used in a variety of preparations and routes of administration, enabling choice for onset, duration of action, and mode of delivery

The opioid antagonist alvimopan has been demonstrated to reduce the incidence of postoperative ileus and accelerate GI function without compromising opioid analgesia in patients undergoing bowel resection (Ludwig 2008)

Most clinical trials showing benefits of intramuscular strong opioids use nurse-administered regimens. In regular clinical practice, full adherence to nurse-administered regimens is not usually achievable, and the full analgesic benefits of intramuscular strong opioids are also not achieved

Intramuscular administration of strong opioids is considered to be more painful than intravenous administration; however, the dose and rapidity of intravenous administration should be assessed to minimise the risk of respiratory depression

Transferable Evidence from Other Procedures - Study information

Three out of five studies showed a significant benefit of IV PCA over IM regular/PRN administration of strong opioids for reducing postoperative pain scores in patients undergoing abdominal hysterectomy Click here for more information

Evidence for a benefit of PCA compared with regular/PRN IM administration of strong opioids for reducing overall opioid consumption is inconsistent, although one study suggests that they produced different patterns of dosing in patients undergoing abdominal hysterectomy Click here for more information

Opioids administered by PCA improved analgesia, decreased the risk of pulmonary complications and patients preferred them compared with regular IM, IV or SC opioid treatment, as determined in a quantitative systematic review of randomised trials in various surgical procedures

Open Colonic Resection-Specific Evidence - Study information

IM regular or PRN morphine was superior to IV PCA morphine for reducing daily opioid use (both p<0.05) and the total amount of opioid used in two studies (no statistics provided, n=41; p<0.05, n=62)

IM morphine was similar to PCA morphine for the frequency of PONV in one study reporting this parameter (n=41)

IM morphine was similar to PCA morphine for the level of postoperative pain and activity (measured by patient questionnaire), frequency of PONV, level of sedation and the duration of ileus and of hospital stay. However, this study did not record pain on a linear scale (n=62)

A systematic review found that the combination of codeine with paracetamol was associated with an increase in drowsiness and dizziness compared with paracetamol alone

A systematic review found an increased incidence of central nervous system adverse effects with paracetamol plus dextropropoxyphene compared with placebo

Open Colonic Resection-Specific Evidence - Study information

Administration of IV tramadol immediately after peritoneal closure, or immediately following surgery extended the time to first analgesic request compared with pre-operative administration (p<0.01; n=90)

PROSPECT Recommendations

Paracetamol is recommended for pain of moderate- (>30 VAS <50) or low- (VAS =30) intensity, in combination with COX-2-selective inhibitors or conventional NSAIDs (Grade B), based on its mild analgesic and opioid-sparing effect in transferable evidence (LoE 1), only for patients who do not receive epidural analgesia or with cessation of epidural analgesia (Grade D, LoE 4)

However, paracetamol is not recommended for high-intensity pain (VAS =50 mm) (Grade B) because it has no additional analgesic benefit over that conferred by conventional NSAIDs in transferable evidence (LoE 1)

Clinical Practice

Paracetamol is a well-established analgesic for low- (VAS=30) or moderate- (VAS>30<50) intensity pain and has a favourable safety profile

If paracetamol is used as part of a multi-modal regimen, the anti-pyretic effect can mask complications such as anastomotic leakage

Transferable Evidence from Other Procedures - Study information

Paracetamol was superior to placebo for reducing postoperative pain scores, but produced reductions in VAS scores of <13 mm Click here for more information

Paracetamol was superior to placebo for reducing supplementary analgesic consumption within 0–24 h in patients undergoing abdominal hysterectomy Click here for more information

Paracetamol combined with weak opioids (codeine, tramadol) is superior to weak opioids alone in a review of dental, gynaecological and orthopaedic surgery

A meta-analysis of randomised controlled trials showed that paracetamol combined with PCA morphine induced a significant morphine-sparing effect but did not change the incidence of morphine-related adverse effects in the postoperative period

There is evidence that concurrent use of paracetamol and conventional NSAIDs improves pain relief compared with paracetamol alone, but there is no evidence for a superior analgesic effect of the combination compared with conventional NSAIDs alone

One study showed a marginal but significant benefit of rectal diclofenac over rectal paracetamol for reducing average pain scores over 24 h, (p=0.008; n=44) in patients undergoing abdominal hysterectomy

In a systematic review of a variety of surgical procedures, paracetamol plus NSAID conferred no significant benefit over NSAID alone for reducing pain scores in orthopaedic and gynaecological operations. However, a significant benefit was seen in the lower-intensity pain associated with dental operations

Open Colonic Resection-Specific Evidence

PROSPECT Recommendations

Continuous epidural anaesthesia and postoperative analgesia is recommended for routine use in colonic resection (Grade A), based on its benefits for reducing postoperative pain, systemic opioid use and improving bowel recovery time (procedure-specific evidence, LoE 1)

A combination of epidural local anaesthetic (LA) and strong opioid is recommended for epidural analgesia (Grade A), based on procedure-specific evidence of their combined efficacy, in reducing postoperative pain and systemic opioid use, compared with LA alone (LoE 1). However, the addition of opioid to epidural LA results in an increase in time to first bowel movement (LoE 1)

Clinical Practice

Thoracic epidural is considered to be more appropriate than lumbar epidural for anaesthesia and analgesia in open colon surgery

Epidural analgesia is associated with a relatively high degree of patient monitoring and rare major complications

Clonidine is not used routinely because it is associated with an increased risk of hypotension, sedation and bradycardia

Transferable Evidence from Other Procedures - Study information

Epidural analgesia using LA was superior to systemic strong opioid for reducing postoperative pain scores in six studies identified in a systematic review of abdominal surgery

Epidural analgesia using a combination of LA and strong opioid was superior to epidural LA alone for reducing postoperative pain – 15 mm reduction in VAS score on a 100-mm scale – in a meta-analysis of five studies in abdominal surgery

Epidural analgesia using LA was superior to epidural opioids or systemic opioids for reducing the incidence of postoperative gastrointestinal paralysis, in a systematic review in abdominal surgery

Epidural LA was suggested to be the most effective method of reducing ileus and improving postoperative catabolism in patients undergoing abdominal surgery Click here for more information

Results for the incidence of postoperative nausea were inconsistent for comparison of epidural LA with epidural LA plus opioid, and no significant difference for the incidence of vomiting was seen Click here for more information

Postoperative thoracic epidural analgesia was superior to postoperative PCA for reduction of VAS pain scores at Day 2 (p=0.01; n=59), but there was no significant difference between the groups at discharge, or on Days 1, 10 and 30

Two studies demonstrated that epidural bupivacaine conferred a benefit over general anaesthesia and systemic analgesia for reducing postoperative pain scores at rest for 1–72 h in one study (all p<0.05; n=116)

Mean summary area under the curve (AUC) of VRS pain scores at rest for 0–72 h postoperatively was significantly lower with PCEA, compared with continuous epidural analgesia (p<0.001; n=205), and median summary VRS pain scores on movement for 24–72 h postoperatively were significantly lower in the PCEA group compared with the continuous epidural group (p<0.001; n=205)

A significantly higher proportion of patients in the PCEA group were 'very satisfied' with the treatment compared with the continuous epidural infusion group at 72 h postoperatively and at discharge (both p<0.0001; n=205)

Epidural LA plus strong opioid showed no difference in the incidence of nausea and vomiting compared with GA plus systemic analgesia in four studies Click here for more information

A meta-analysis of randomised studies performed to compare the effect of local anaesthetic epidural analgesia with parenteral opioid analgesia in patients undergoing colorectal surgery, found no significant difference in the incidence of PONV (5 studies analysed; n=189), anastomotic leakage (7 studies analysed; n=459), or length of hospital stay (n=716)

Postoperative thoracic epidural analgesia conferred no significant benefit over postoperative PCA for reducing the time to first bowel movement (n=34 analysed)

There was no significant difference in patient quality of life or satisfaction with hospital stay scores between the groups receiving postoperative thoracic epidural analgesia and postoperative PCA (n=59)

There was no significant difference between the postoperative thoracic epidural analgesia group and postoperative PCA group for a return to normal levels of activities at discharge, 10 days and 30 days postoperatively ((n=59)

PROSPECT Recommendations

Continuous postoperative wound infusion with LA is not recommended (Grade D, LoE 4) as procedure-specific evidence is limited and inconsistent

Pre-closure wound infiltration with local anaesthetic is not recommended for open colonic resection (Grade D, LoE 4), due to lack of procedure-specific evidence and inconclusive transferable evidence from other large abdominal surgeries

Clinical Practice

Continuous pre-peritoneal infusion of LA may be considered as an alternative when epidural analgesia is not feasible or contraindicated based on limited procedure-specific evidence for analgesic benefit (LoE 2)

Intra-operative wound infiltration is a well-established method of analgesia with a favourable safety profile. However, methods of postoperative wound infusion are not well established

Five of eight studies showed no significant benefit of intra-operative wound infiltration over placebo for reducing postoperative pain scores following abdominal hysterectomy Click here for more information

A systematic review of incisional local anaesthesia showed that evidence of analgesic efficacy in hysterectomy (4 studies), open cholecystectomy (8 studies) and a variety of other surgical procedures (9 studies) was inconclusive Click here for more information

Continuous pre-peritoneal infusion with ropivacaine was superior to placebo for reducing the time to hospital discharge (p=0.02) (n=42)

Continuous wound infusion with lidocaine and bupivacaine conferred no benefit over intermittent IV morphine infusion for reducing time to first bowel movement, time to first flatus and timing of postoperative mobilisation (n=70)

Continuous wound infusion with lidocaine and bupivacaine was associated with a similar incidence of vomiting compared with intermittent IV PCA morphine infusion (n=70)

Continuous wound infusion with 0.54% ropivacaine conferred no significant benefit over placebo for reducing PCA morphine use on postoperative Days 1, 2 and 3 (n=310 analysed)

Continuous wound infusion with ropivacaine conferred no significant benefit over placebo for reducing the length of hospital stay (n=310)

Continuous wound infusion with ropivacaine had no significant effect on the incidence of postoperative nausea and vomiting, compared with placebo (n=42)

Pre-peritoneal continuous infusion with ropivacaine had no significant effect on the incidence of postoperative nausea and vomiting, compared with placebo (n=310)

Continuous wound infusion with 0.54% ropivacaine conferred no significant benefit over placebo for the reduction of VAS mobility scores on postoperative Days 1,2, and 3 (n=310)

PROSPECT Recommendations

Care protocols (which include controlled rehabilitation with early ambulation and diet, or multi-modal optimisation programmes) following colonic resection are recommended (Grade A) based on factors other than the management of postoperative pain (e.g. postoperative ileus (procedure specific LoE 1) and length of hospital stay (procedure specifc LoE 1)), as postoperative pain benefits are inconsistent (LoE 4). Controlled studies are necessary to define the influence of the various components

The 'anti-inflammatory regimen' (GA combined with spinal, epidural, IV corticosteroid and NSAID) is not recommended over GA + IV opioid analgesia (Grade D, LoE 4) because of limited evidence in colonic resection. Moreover, it introduces an increased level of complexity

Clinical Practice

Epidural anaesthesia combined with general anaesthesia is used routinely for colonic resection, except in patients with contra-indications to epidurals, where general anaesthesia alone is used.

Nasogastric tubes should be removed as early as possible to avoid gastroparesis.

A meta-analysis showed that omitting nasogastric tubes conferred a significant benefit over their use for reducing the time to first oral intake, pulmonary complications, fever, atelectasis and pneumonia

A meta-analysis showed that patients managed without nasogastric tubes had significantly greater abdominal distension and vomiting

Care by CREAD did not confer a benefit over TRAD care for reducing postoperative pain scores on Days 2, 10 or 30 (n=64)

Care by CREAD showed that pain scores evaluated by the McGill pain questionnaire were higher at discharge but were equal on postoperative Day 10 compared with care by TRAD (p<0.02; n=64)

Mechanical massage with aspiration of abdominal wall and mechanical massage without aspiration groups both demonstrated similar Hamilton anxiety scores at the end of the study (n=50)

Mechanical massage with aspiration of abdominal wall and mechanical massage without aspiration groups had a similar time to discharge from hospital (n=50)

Gastrostomy and nasogastric tubes were associated with similar postoperative pain scores (n=107)

Postoperative restriction of IV fluids did not confer any benefit over the standard IV fluid regimen for reducing VAS pain scores at rest or during movement during the hospital stay (n=80)

Postoperative restriction of IV fluids did not confer any benefit over the standard IV fluid regimen for reducing the consumption of postoperative supplementary analgesics (n=80) Click here for more information

Postoperative restriction of IV fluids did not confer any benefit over the standard IV fluid regimen for reducing the incidence of postoperative nausea and vomiting (n=80)

Time to passage of first flatus was similar for patients allocated to the restricted postoperative IV fluid and standard postoperative IV fluid regimens (n=80)

Postoperative restriction of IV fluids conferred no significant benefit over the standard postoperative fluid regimen for reducing the time to medical discharge or hospital discharge (n=80)

PROSPECT Recommendations

Clinical Practice

Conventional NSAIDs are used in preference to strong opioids in laparoscopic procedures

Transferable Evidence from Other Procedures

Conventional NSAIDs have proven analgesic efficacy in a variety of surgical procedures

A meta-analysis of randomised controlled trials that was performed to evaluate the risk of morphine-related adverse effects in patients treated with NSAIDs demonstrated that NSAIDs decreased the incidence of nausea, vomiting and sedation, but not pruritus, urinary retention or respiratory depression

Six out of eight studies showed a significant benefit of postoperative conventional NSAIDs compared with placebo for reducing postoperative pain scores in patients undergoing hysterectomy Click here for more information

Conventional NSAIDs conferred a significant benefit over placebo for reducing supplementary analgesia requirements over 24 h or more in patients undergoing abdominal hysterectomy Click here for more information

Conventional NSAIDs were superior to placebo for reducing morphine consumption in abdominal surgery but did not consistently reduce pain scores in two studies in abdominal surgery Click here for more information

One randomised trial in patients undergoing transurethral prostatectomy showed that diclofenac did not affect total blood loss compared with placebo

Two of three studies showed no significant analgesic benefit of conventional NSAIDs plus epidural analgesia compared with epidural analgesia alone Click here for more information

Results were inconsistent for conventional NSAIDs compared with placebo for the time to first analgesic request following abdominal hysterectomy Click here for more information

Conventional NSAIDs and placebo were not significantly different for the incidence of PONV (all groups received background strong opioid) in patients undergoing abdominal surgery Click here for more information

Diclofenac 50 mg IM bolus pre-operatively then postoperatively at 4 and 10 h, plus epidural analgesia using bupivacaine 0.5% continually infused at 8 mL/h did not confer a benefit for extending the time to first analgesic request compared with epidural analgesia alone in patients undergoing abdominal hysterectomy (n=26)

Randomised endoscopic trials in healthy volunteers have shown that COX-2-selective inhibitors are associated with a lower incidence of upper gastrointestinal ulceration compared with conventional NSAIDs for short-term use

Conventional NSAIDs and COX-2-selective inhibitors have been associated with an increased risk of transient hepatotoxicity. Cases of acute hepatic failure have also been reported. Elderly females, with autoimmune disease, and taking other potentially hepatotoxic drugs, may be most susceptible

Short-term use of conventional NSAIDs or COX-2-selective inhibitors can increase the risk of transient renal impairment, especially in patients with existing renal dysfunction, and both types of agent have been associated with cases of acute renal failure in high-risk patients

Postoperative IV ketorolac was superior to placebo for reducing the time to first flatus (p=0.005; n=44)

Postoperative IV ketorolac significantly reduced the time to return to full diet, compared with placebo (p=0.033; n=44)

VAS pain scores on coughing were significantly greater with IV ketorolac, compared with placebo at Day 4 (p<0.001), but there was no significant difference between the groups on Days 1, 2, and 3 (n=44)

There was no significant difference between the IV ketorolac and placebo groups for VAS pain scores at rest on Days 1–4

There was no significant difference in the length of hospital stay between the postoperative IV ketorolac and placebo groups (n=44)

There was no significant difference in the incidence of anastomotic leaks in the IV ketorolac and placebo groups (n=44)

PROSPECT Recommendations

Clinical Practice

Further evidence is needed to precisely define the role of IV lidocaine in this setting, including direct comparisons with epidural analgesia

IV lidocaine may induce hypotension

If IV lidocaine is used, it is recommended that safety data are taken into account

Transferable Evidence from Other Procedures

A meta-analysis of randomised clinical trials performed to evaluate the effect of continuous IV lidocaine infusion during and after abdominal surgery, reported that lidocaine significantly reduced postoperative VAS pain scores, duration of postoperative ileus, incidence of PONV and length of hospital stay, compared with the controls

Laparoscopic Colonic Resection-Specific Evidence

Continuous intra-/postoperative IV lidocaine was superior to placebo for reducing postoperative pain scores during mobilization and on coughing Click here for more information

Clinical Practice

The risk of side-effects associated with epidural analgesia may outweigh the benefits of analgesia in laparoscopic colonic resection

Transferable Evidence from Other Procedures

None cited

Laparoscopic Colonic Resection-Specific Evidence

Two of two studies showed that epidural LA plus opioid was superior to IV PCA morphine for reducing postoperative pain scores Click here for more information

One study showed that thoracic epidural LA + opioid was associated with significantly lower VAS fatigue scores on postoperative Day 3 (p=0.025), compared with IV PCA morphine, although there was no significant difference between the groups on Days 1, 2 and 4

One study found that thoracic epidural LA + opioid was superior to IV PCA opioid for reducing postoperative vomiting on Days 1 and 2 (p=0.033 and p=0.005; n=50), but not on Days 3 or 4

One study showed that time to first flatus and first bowel movement was significantly shorter with thoracic epidural LA + opioid, compared with IV PCA morphine (p=0.0061 and p=0.0027, respectively; n=50)

One study reported that time taken to return to fluid diet and full diet was significantly shorter for patients in the thoracic epidural LA + opioid group, compared with the IV PCA group (p=0.0442 and p=0.0436, respectively; n=50)

Thoracic epidural ropivacaine + IV PCA morphine was superior to IV PCA opioid alone, for reducing the amount of supplementary IV PCA morphine administered between surgery to Day 2 (p=0.04). However, there was no significant difference between the groups from Day 2–4, or from surgery to Day 4 overall (n=20)

VAS pain scores during Days 1–8 were significantly lower in the group receiving GA + thoracic epidural analgesia, compared with the group receiving GA alone (p=0.004; n=75 overall)

GA + thoracic epidural analgesia was associated with a significantly shorter time to recovery of GI function (GI-3) and time to first bowel movement (p=0.025 and p=0.038, respectively; n=75), compared with GA alone, but there was no significant difference for time to first flatus or time to solid food tolerance

One study reported that the incidence of postoperative nausea was similar in patients receiving thoracic epidural LA + opioid and IV PCA opioid (n=50)

One study reported that the incidence of nausea requiring antiemetics, urinary retention, hypotension, and respiratory depression was similar in the groups receiving thoracic epidural LA + opioid and IV PCA morphine (n=38)

Two studies of two reported no significant difference in the length of hospital stay between the groups receiving thoracic epidural LA + opioid or PCA IV morphine (n=38)

Thoracic epidural ropivacaine + IV PCA morphine did not confer any significant benefit for reducing VAS pain scores at rest, or during coughing, from surgery to Day 4, or the time to first bowel movement, compared with IV PCA morphine alone (n=20)

The incidence of postoperative nausea and vomiting, frequency of naso-gastric tube reinsertion and length of hospital stay was similar between the groups receiving GA + thoracic epidural analgesia or GA alone (n=75 overall)

PROSPECT Recommendations

The combination of spinal analgesia and general anaesthesia is not recommended (Grade D) as the risk:benefit balance is not positive (LoE 4), and because of limited procedure-specific evidence

Clinical Practice

Spinal analgesia (LA + opioid) has a limited duration of action

Spinal morphine may produce some postoperative pain relief but also produces risk of PONV and prolongation of postoperative ileus, and limited duration of analgesic effect

Transferable Evidence from Other Procedures

One study showed that spinal analgesia with fentanyl + LA was superior to spinal analgesia with LA alone for reducing postoperative pain scores during from 0–8 h, but not between 8–24 h, following abdominal hysterectomy (n=20 overall)

The same study found spinal fentanyl + LA was superior to spinal LA alone for reducing the time to first analgesia request; the i